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Essential oils EOs are comprised of a complex mixture of volatile phytochemicals from diverse classes including monoterpenes, sesquiterpenes, and phenylpropanoids. Numerous researchers have studied the antibacterial, antifungal, antioxidant, and antiviral properties of EOs.
These EOs are found to be active against a wide variety of viruses, such as influenza virus IFVhuman herpesviruses HSVhuman immunodeficiency virus HIVyellow fever virus, and avian influenza Ma and Yao HSV -1 and -2 are known to cause many life-threatening diseases in humans and are one of the major reasons for mortality in immunocompromised patients.
HSV-1 is majorly responsible for HSV-induced lesions in the oral cavity and epidermis, while HSV-2 causes genital herpes, a sexually transmitted disease. An in vitro study conducted by Schnitzler and colleagues showed that lemon balm oil inhibited plague formation of HSV-1 and HSV-2 viruses in a dose-dependent fashion.
Moreover, at higher concentrations it abolished the viral infectivity almost completely Schnitzler et al. Pre-treatment with EOs obtained from illicium verum, Melaleuca alternifoliaLeptospermum scopariumand Matricaria recutita was found to inhibit the infective ability of acyclovir-sensitive and -resistant HSV stains, indicating the immense antiviral potential of EOs Schnitzler et al.
Anti-IFV properties of liquid and vapour forms of EOs obtained from various plant species were studied using in vitro techniques. Vapours of EOs obtained from Citrus bergamiaEucalyptus globulusand their isolated compounds, i. citronellol and eugenol showed rapid anti-IFV actions.
While in liquid form, EOs obtained from Cinnamomum zeylanicumCitrus bergamiaCymbopogon flexuosusand Thymus vulgaris showed better anti-IFV properties i.
Vapour form of EOs was also found to be safe against monolayers of epithelial cells. The study concluded that EOs in vapour form could benefit people suffering from influenza Vimalanathan and Hudson Carvacrol and its isomer thymol obtained from oregano have been shown to inhibit viral host cell fusion via depletion of viral cholesterol from the HIV-1 envelope membranes, thus blocking the entry of the virus into the host system Mediouni et al.
Owing to the lipophilic nature of EOs, these have the potential to intercalate into the lipid double layer of the viral envelope.
Subsequently, the fluidity of the membranes is changed and, at a higher concentration, the membranes are even ruptured Wink Major mechanisms through which EOs induce antiviral actions are, direct actions on free viruses, inhibition of steps involved in virus attachment, penetration, intracellular replication, and release from host cells and inhibition of vital viral enzymes Ma and Yao ; Schnitzler et al.
In this regard, research activities were conducted to check the anti-SARC-CoV-2 efficacies of EOs. The current review compiles available scientific information about the possible beneficial effects of EOs in COVID The current review provides precise and comprehensive information on the essential oils and their possible contribution in the prevention and treatment of COVID The study database encompassed articles of peer-reviewed journals, books, thesis, dissertations, various patents, and supplementary reports covering anti-SARC-CoV-2 properties of traditionally used essential oils.
Essential oils having scientifically established antiviral activities against SARC-CoV-2 in in vitro, docking models, or in clinical settings were selected for reporting. Essential oils having antiviral activities against other viruses and lacking any scientific evidence against SARC-CoV-2 were excluded.
Enveloped viruses are known to respond sensitively to essential oils Schnitzler et al. Essential oils obtained from eucalyptus Eucalyptus globulus are traditionally used to treat various respiratory ailments including pharyngitis, bronchitis, and sinusitis.
Eucalyptus oil and its active constituent, 1,8-cineole have been shown to exhibit muscle relaxant effects by decreasing smooth muscle contractions of airways induced by different agents Bastos et al. Moreover, clinical studies have indicated that inhalation of cineole extracted from eucalyptus exerted anti-inflammatory by blocking cytokines release and analgesic effects; hence, it can be effectively used in COPD and asthmatic patients Juergens et al.
Eucalyptus oil is reported to have in vitro antiviral activities against various strains of viruses including enveloped mumps viruses MV and herpes simplex viruses HSV-1 and HSV-2 Lau et al.
Brochot and colleagues also reported the antiviral activities of eucalyptus oil and its active constituent, i. Both essential oil and 1,8-cineole were proposed to inactivate free influenza A virus and disrupt the envelope structures of virus Brochot et al. Having established the antiviral activity of eucalyptus oil and eucalyptol against respiratory viruses, multiple researchers have attempted to explore the antiviral efficacy of eucalyptus oil and its active ingredients against SARC-CoV-2 using in vitro assays and molecular docking techniques.
Data obtained showed that jensenone formed complex with Mpro via hydrophobic interactions with ALA7, PRO52, TRP, LEU29, TRY, and PRO; hydrogen bond interactions with M4, V18, L30, D10, and T16; and ionic interactions with LYS3, ASP34, ARG38, and HIS Sharma and Kaur a.
Sharma and colleagues also predicted preprints the anti-proteinase efficacy of 1,8-cineole eucalyptolanother active constituent of eucalyptus oil, using molecular docking techniques. Data obtained showed that 1,8-cineole can bind with Mpro and thus can inhibit viral reproduction.
Among these two compounds, 1,8-cineole is more extensively studied for its pharmacological potentials against various respiratory ailments Juergens et al.
Juergens and colleagues conducted a double-blind clinical trial to check the efficacy of 1,8-cineole in steroid-dependent bronchial asthma patients. A recent review highlighted the favourable safety and efficacy profile of eucalyptol 1,8-cinoele in numerous multi-centre, double-blinded, and randomized clinical trials conducted in Germany in patients having acute and chronic respiratory conditions including rhinosinusitis, bronchitis, COPD, and asthma, respectively Juergens et al.
A study conducted by Merad and colleagues showed that almost all COVID positive patients have lung abnormalities. Abnormal and overactive inflammatory responses to SARS-CoV-2 are proposed to be the major causes of disease severity and death in COVID patients. This hyper-inflammatory state is associated with increased levels of circulating cytokines, profound lymphopaenia, and substantial mononuclear cell infiltration in the lungs and other organs including heart, spleen, lymph nodes, and kidneys.
The systemic cytokine profiles observed in patients showed increased production of cytokines such as IL-6, IL-7, and tumour necrosis factor TNF and many other pro-inflammatory cytokines Merad and Martin Various in vitro and ex vivo studies were conducted to study the effects of eucalyptus oils and eucalyptol treatments on monocytes and macrophage recruitment in response to lung inflammation and infections.
Data of these studies demonstrate marked immunomodulatory properties of both eucalyptus oil and its active ingredient, i. Both treatments reduced the release of pro-inflammatory cytokines from monocytes and macrophages, but their phagocytic properties were not halted Juergens et al.
Eucalyptol is also known to have mucolytic and bronchodilatory properties Juergens et al. Interestingly, eucalyptus oil has also been shown to have disinfection properties and inhibited the growth of viruses on various utensils and filter devices Usachev et al.
Taken together, data from both preclinical and clinical trials point towards the promising therapeutic potential that resides in eucalyptus oil and its active constituent, i. eucalyptol in the prevention and treatment of COVID Therefore, further studies are urgently warranted in this regard.
Garlic has been used as a medication to treat common cold, influenza, and other kinds of infections for centuries. Garlic oil was chemically analysed by the GC—MS method and 18 compounds were identified, out of which allyl disulphide ACE2 is involved in the viral invasion of host cells, while Mpro is involved in viral replication.
All the 17 compounds studied showed interactions with host protein ACE2 as well as with viral proteases, indicating that garlic oil has great potential to treat COVID patients Thuy et al. Virus-induced oxidative stress plays a critical role in the viral life cycle as well as in the pathogenesis of viral diseases.
This leads to the activation of host antioxidant pathways including nuclear factor erythroid 2prelated factor 2 Nrf2 Lee Nrf2 transcription factor is known to control the expression of various genes involved in antiviral actions McCord et al.
A study conducted by McCord and colleagues showed that potent Nrf2 activation by PB ® compound downregulated ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. Both of these proteins are recognized to play a major role in the entry of SARS-CoV-2 into host cells.
The authors suggested that Nrf2 activation may significantly decrease the intensity of the cytokine storm in COVID patients McCord et al. Diallyl sulphide DASone of the active constituents of garlic, has been shown to induce Nrf2 activation in lung MRC-5 cells.
Thus, on the basis of these docking and in vitro studies, it is proposed that garlic essential oils and their isolated constituents, especially DAS, have potential to prevent the entry of virus into host cells as well as to activate molecular antioxidant pathways that decrease the secretions of culprit pro-inflammatory cytokines.
: Antiviral virus-fighting properties| If You Get Sick with COVID, Antiviral Treatments Can Protect You Against Severe Illness | CDC | Aqueous extract of whole plant properyies been Sleep hygiene to inhibit propertoes DNA pro;erties of HBV and woodchuck Antiviarl virus WHV Tan et al. Attack Hydration for staying hydrated during illness Basic reproduction number Compartmental Hydration for staying hydrated during illness in Upper body muscular endurance Critical community size Force of infection Herd immunity Infection rate Serial interval. Graphene oxide: a nonspecific enhancer of cellular growth. We avoid using tertiary references. Despite their successes, in the United States there exists plenty of stigma surrounding vaccines that cause people to be incompletely vaccinated. Antiviral activities of extracts and selected pure constituents of Ocimum basilicum. COVID, considered as the deadliest viral infection in present time worldwide. |
| Use Antiviral Herbs to Boost Immune System and Fight Viruses | About 8 species of this genus are found in Bangladesh, namely Ocimum tenuiflorum L. which have been reported extensively for diverse antiviral activities. This medicinal plant is found almost every yard of people in Bangladesh. It produces a number of antiviral bioactive compounds, such as ursolic acid, eugenol, 1,8-cineole, and rosmarinic acid which exhibit potential to inhibit HSV-I and II Caamal-Herrera et al. basilicum , known as sweet basil, contains 1,8-cineole, camphor, thymol, eugenol, eugenol epoxide, apigenin, linalool, and ursolic acid which have been reported to work against HIV-I, HSV, ADV-3, 8, 11, HVB, EV, and CVB-I Behbahani et al. gratissimum is an aromatic herb which is commonly known as African basil. Essential oil of this basil leaves contains two alcohols namely eugenol and thymol. Eugenol inhibits replication of HSV-I and II while thymol destructs the virion of HSV-I Benencia and Courreges, ; Maria das Graças et al. β-caryophyllene and 1,8-cineole have been isolated from O. campechianum which exhibit anti-HSV-I and II activities as well as inhibit infectious bronchitis virus IBV Maria das Graças et al. americanum , recognized as American basil, is a medicinal plant which can produce essential oils and found in Bangladesh. Rosmarinic acid and oleanolic acid are the essential oils isolated from this herb. Oleanolic acid inhibits HIV-I protease whereas rosmarinic acid inhibits internal ribosome entry site of EV Aluko et al. africanum produces caffeic acid which inhibits the multiplication HSV-I. Beside, linalool has also been isolated from the essential oil of this medicinal plant havinganti-ADV activity Romeilah et al. forsskaolii is known as wild Amazonian basil which produces ursolic acid which exhibits anti-HCV activity. Moreover, O. carnosum showed anti-HSV-I and II activities due to presence of trans-anethole which inhibits multiplication of HSV-I and II Tshilanda et al. Azadirachta indica A. This medicinal plant has a lot of medicinal properties and so, has been used for health management from ancient time in folklore, Ayurvedic, and Unani medicinal systems. indica bark remarkably blocked the entry of HSV-I into host cells. Virucidal activity against CVB-B4 was observed by the extract of A. indica leaves Alzohairy, Gedunin and pongamol are the antiviral biocompounds extracted from A. indica having activity against DENV. Gedunin showed significant binding affinity to NS3 RNA polymerase and NS3 protease helicase mediate the synthesis of DENV proteins and genetic materials in the host cell as well as capsid and envelope proteins required for entry of DENV into host cells Rao and Yeturu, Melia azedarach L. is another antiviral medicinal plant from Meliaceae family which has been reported for inhibitory activities against vesicular stomatitis VSV and HSV-I. A meliacarpin named limonoid 1-cinnamoyl-3,dihydroxymeliacarpin has been isolated from ethyl acetate extract of the leaves of this plant which showed inhibitory activities against VSV IC 50 values of 6 μM and HSV-1 IC 50 values of 20 μM Alché et al. Ficus religiosa L. belongs to the family Moraceae which is used in traditional Ayurvedic and Unani medicines for healing cough, wheezing and asthma as well as sexually transmitted infections like gonorrhea and genital ulcers. This medicinal plant exhibits numerous antiviral activities. A study demonstrated that ethanolic extract of the bark of F. religiosa inhibited Human rhinoviruses HRV EC 50 value: 5. Aqueous extract showed inhibitory activity against respiratory syncytial virus RSV EC 50 value: 2. Another study stated that aqueous and chloroform extracts of bark were active against HSV-II and acyclovir-resistant strain. The underlying mechanism of the aqueous extract involved direct inactivation of viral activity whereas chloroform extract suppressed the attachment and entry of virus to host cell membrane along with inhibition of viral progeny formation Ghosh et al. Artocarpus genus is another source of antiviral medicinal plant species. Artocarpus integer Thunb. Zorn Fosberg are the species of this genus which have antiviral activity. integer has been reported to have activity against rotavirus simian rotavirus, SA11 and human rotavirus, HCR3 strains Gonçalves et al. Another study showed that dichloromethane extract of the leaves of A. heterophyllus showed strong anti-HCV IC 50 value: 1. altilis and A. camansi showed moderate anti-HCV activities IC 50 values: 6. The underlying mechanism of such potent anti-HCV activity of A. heterophyllus involved synergistic effects such as direct virucidal activity inhibition of viral entry and inhibition of replication of RNA and expression of viral protein at higher concentration Hafid et al. Phyllanthus niruri L. This plant possesses antiviral activity as well. Aqueous extract of whole plant has been reported to inhibit endogenous DNA polymerase of HBV and woodchuck hepatitis virus WHV Tan et al. Another study stated that ethanolic extract of P. niruri has Anti-HCV activity IC 50 value: 4. Apart from this, it showed synergistic activity 4-fold with an established drug, a NS3 protease inhibitor named simeprevir. Phyllanthin and hypophyllantin have been identified from this plant which showed binding to a protein, 4GAG required for entry of HCV to host cells in a in silico molecular docking assay Wahyuni et al. Piper longum L. and Piper nigrum L. are the two most common species of Piperaceae family which are cultivated in Bangladesh as spices of cooking. Both of these species exhibit a number of medicinal properties and thus, are used as folklore and traditional medicines from primordial times. Seeds of these medicinal plants have been reported for inhibitory activities on vesicular stomatitis indiana virus VSV-IN and human para influenza virus PIV Priya and Saravana Kumari, longum contains piperine which is a potent anti-HBV compound functioning against the secretion of HBsAg Selectivity Index, SI: Furthermore, P. nigrum contains guaiol which has been reported by an in silico study to possess inhibitory potential to 6LU7 and 7JTL crucial targets of coronavirus Pandey et al. Cynodon dactylon L. is a non-toxic and edible grass belonging to Poaceae family which is known as durva grass or Bermuda grass It is found all over the countryside of Bangladesh and used as expectorant, emetic, laxative, coolant, analgesic, aphrodisiac, alexipharmic, emmenagogue, and so others. This medicinal plant is very effective against bovine coronavirus infection BCoV which functions by inhibiting protease enzyme. As this viral strain has some common features with SARS-CoV and SARS-CoV-2, it can be used as dietary intervention of COVID Nalanagula, Rosa centifolia L. The leave of this plant has antiviral activity. Methanolic extract of the leaves of R. centifolia L showed anti-HIV activity Palshetkar et al. Hedyotis scandens Roxb. is a medicinal plant of Rubiaceae family found in tribal hill area of Bangladesh. This plant is used as folklore medicine in Chakma tribe. Two antiviral bioactive compounds have been isolated from ethanolic extract of the whole plant namely maltol b-D-apiofuranosyl-b-D-glucopyranoside, and grevilloside G. These phytocompounds showed anti-RSV activity. Aegle marmelos L. Corrêa, a member of Rutaceae family, is a food producing plant which is found everywhere in Bangladesh. It is commonly known as bael or stone apple or wood apple. In Ayurveda, various parts of this plant are used because of having antidiarrhoeal, antimicrobial, antiviral, radioprotective, anticancer, chemopreventive, antipyretic, ulcer healing, antigenotoxic, diuretic, antifertility, and anti-inflammatory properties. This plant produces a bioactive compound named seselin having activity against multiple targets of SARS-CoV In silico molecular docking study showed that seselin has inhibitory potential to the receptors SARS-CoV-2S protein binding energy: 6. A number of citrus fruits producing medicinal plants namely Citrus limon L. Osbeck, Citrus sinensis L. Osbeck, and Citrus paradisi Macfad. are also found in this family which are commonly known as lemon, orange and grapefruit sequentially. All of them are very rich sources of vitamin C which fastens healing of COVID by boosting immunity Bellavite and Donzelli, Essential oils extracted from the fruits of these medicinal plants have been reported for having inhibitory potential to HAV Battistini et al. Potent antiviral compounds named hesperidin and luteolin have been isolated from fruit of C. An in silico study has demonstrated that hesperidin showed efficacy to inhibit spike protein and Mpro that modulate the immature proteins pp1a and ppa1b to the complex and functional one to progress replication process of SARS-CoV-2 Bellavite and Donzelli, Furthermore, luteolin has also been reported for having inhibitory activities against ACE2 receptor both of the subtypes AT1 and AT2 and RdRp enzyme by an in silico assay Goyal et al. Camellia sinensis L. Kuntze belonging to the family Theaceae is known as tea or green tea which is considered as the most popular drink in worldwide. In Bangladesh, this plant is cultivated in two fairly divergent ecological zones such as Surma valley in greater Sylhet and Halda valley in Chittagong Mamun, The novel antiviral bioactive compounds namely epigallocatechingallate EGCG , epicatechin gallate ECG and epicatechin EC have been isolated from the leaves of this plant. EGCG has been reported for surprising and divergent antiviral activities. It binds to virion surface proteins and blocks the attachment of HSV-I to heparan sulfate of host cells. It inhibits RNA and DNA synthesis as well as antigen expression in HBV. It has broad-spectrum antiviral activities on HCV, IAV, murine cytomegalovirus mCMV , vesicular stomatitis virus VSV , and reovirus as well. Apart from these, EGCG showed potency to inhibit HIV reverse transcriptase by downregulation of the expression of the HIV p24 antigen. A destructive effect has been observed on HIV-I viral particle. It interferes with HIV-I attachment to host cell surface too. Moreover, DENV, Japanese encephalitis virus JEV , tick-borne encephalitis virus TBEV , Zika virus ZIKV , CHIKV, EV, and rotaviruses are also inhibited by EGCG Xu et al. Boehmeria nivea L. is the only species of Urticaceae family which exhibits antiviral activity. It is found in Bandarban, Khagrachari and Rangamati area of Bangladesh and traditionally used to prevent miscarriage as well as promote the drainage of pus and healing of wound and infections. A study demonstrated that ethanolic extract of the root exhibits anti-HBV activity. The possible mechanism suggested by the author involved potential inhibition of the expression of HBsAg and DNA of HBV Chang et al. Zingiber officinale Roscoe belongs to the family Zingiberaceae which is commonly known as ginger and cultivated in Bangladesh as a prime spice of cooking. In Ayurveda, the rhizome of this herb is used from pre-historic time because of having anti-arthritis, anti-inflammatory, antidiabetic, antibacterial, antifungal, and anticancer properties. Aqueous extract prepared from the freeze dried powder of the rhizome of this herb showed anti-HCV and anti-CHIKV activities. Active metabolites gingeronone A and 6-gingerol, isolated from the rhizome of Z. officinale have been reported for having anti-SARS-CoV-2 activity in molecular docking studies. Besides, 6-gingerol exhibits efficacy to inhibit SARS CoV-2 by interacting viral proteases, RNA binding protein, and Spike protein Rathinavel et al. On the other hand, gingeronone A inhibits main protease 6LU7 and SARS-CoV-2 ORF8 7JTL Pandey et al. Curcuma longa L. is another species of Zingiberaceae family having numerous medicinal properties. It is also a spice used as foodstuff and cultivated in Bangladesh. It is used as herbal medicine for managing rheumatoid arthritis, chronic anterior uveitis, conjunctivitis, skin cancer, small pox, chicken pox, wound healing, urinary tract infection, and cancers. Aqueous extract of the rhizome of this herb has anti-HBV activity. It blocked HBx gene transcription by suppressing HBV enhancer I and X promoter through p53 protein Kim et al. This herb produces curcumin which possesses diverse pharmacological activities. Furthermore, a randomized controlled trial has proved the effectiveness of curcumin for pre-exposure prophylaxis of COVID Table 2. This prophylactic activity may be due to a multiple antiviral mechanisms of action interact directly with viral membrane proteins, disrupt viral envelope, inhibit viral protease, and induce host antiviral response by boosting immunity against numerous types of enveloped viruses as SARS-CoV-2 is a enveloped virus b protection from severe pneumonia by targeting NF-κB, IL-6 trans signal, and HMGB1 pathways , and c safe and well-tolerated in both healthy and diseased human subjects Thimmulappa et al. TABLE 3. Bioactive compounds with antiviral mechanism isolated from medicinal plants. From the ancient times, medicinal plants are considered as one of the major priorities of treating illness. Search of antiviral drugs from plant sources is crucial due to fatality and repeated mutations of viruses. Apart from these, new and deadly viral strains are infecting humans time to time. In the last few decades, advancement of synthetic medicinal chemistry has shed light on discovery of synthetic antiviral drugs. A number of synthetic antiviral drugs have been developed which are effective against numerous viruses. Unfortunately, these drugs produce serious adverse effects for continuous administrations. Moreover, many of the synthetic antiviral drugs are ineffective against mutant or resistant strains of viruses. Therefore, the demand for non-toxic antiviral drugs having efficiency to cure viral infections completely still persists. Due to scientific evidences on antiviral potential of naturally produced compounds and their mild side-effects, researchers place their attention extensively on natural resources, especially on plants to search for bioactive metabolites with potent antiviral activities and adequate drug-properties. Pharmaceuticals and nutraceuticals are also paying attention to herbal preparations by using crude extract, syrup, essential oil, and gel extracted from medicinal plants. Interestingly, in recent years, these industries have manufactured them as commercial drug products to treat specific diseases Table 4. TABLE 4. Available commercial herbal preparations from antiviral medicinal plants in Bangladesh. At present, the outbreak of COVID has turned into an evolving worldwide health crisis. Few years back, ZIKV, EV, DENV, and CHIKV have affected a lot of people. Along with these, HIV infection and its treatment still remain unresolved. About 46 medicinal plants available in Bangladesh have been enlisted to have broad-spectrum antiviral activities against a number of viruses. Though phytochemical profiles of these plants are not yet revealed completely, 36 of bioactive metabolites have been reported to exhibit potential antiviral activities with revealing the underlying mechanisms of their activities. Table 3 showed their sources and potential mechanism of activities. COVID, considered as the deadliest viral infection in present time worldwide. It contains ultra-structural spike proteins on the surface having crown resembled shape corona appearance. The genome of this virus encodes structural, accessory, and non-structural proteins. Nucleocapsid N , spike protein S , membrane protein M , and envelope protein E are the major structural proteins Haake et al. FIGURE 1. Impact of bioactive metabolites derived from Bangladeshi medicinal plants on molecular targets of various steps of multiplication process of SARS-CoV This multiplication process is initiated by viral attachment to host cell surface followed by endocytosis via binding and interaction of viral S protein to angiotensin converting enzyme-2 receptor ACE2 receptor on the host cell surface. Inhibitor of S protein, blocker of ACE2 receptor or interferer of S protein-ACE2 receptor interaction might inhibit viral entry to host cell. A number of in silico studies demonstrated that numerous metabolites derived from Bangladeshi medicinal plants including a hesperidin, seselin, 6-gingerol, and humulene epoxide interacted with and inhibited S protein of SARS-CoV-2 Bellavite and Donzelli, ; Rathinavel et al. These metabolites might be considered for development of potential SARS-CoV-2 entry inhibitors. Apart from these, gingeronone A and guaiol inhibited 6LU7 and 7JTL which are crucial for proteolysis mechanism Pandey et al. The next step involves replication of genomic RNA from 16 types of nonstructural proteins nsp regulated by RNA dependent RNA polymerase RdRp which was inhibited by hesperidin, luteolin, quercetin, ECG, and humulene epoxide Goyal et al. According to latest researches regarding drug development against SARS-CoV-2 virus, ACE2 receptor blockers as well as RdRp enzyme inhibitors are considered as the most important candidates. Currently, hesperidin is under phase-II clinical trials for treatment of COVID due to its potential activities against these two major targets. Besides, curcumin and 6-gingerol have been reported for inhibiting this replication process Khaerunnisa et al. After translation and post-translational maturation, the genomic RNA and proteins get assembled, and initiated exocytosis mechanism resulting apoptosis of host cell. HIV, considered as one of the most fatal virus which causes acquired immunodeficiency syndrome AIDS. Thus, invention of antiretroviral therapy to combat this virus remains one of the global challenges to researchers. Multiplication of this virus involves several basic steps, such as attachment to host cell surface, entry and uncoating of genetic materials to the host cell, reverse transcription of genomic RNA with the help of reverse transcriptase RT enzyme followed by translocation of the DNA to host nucleus. Then, the viral DNA gets integrated into host genome and undergoes transcription resulting formation of mRNA and genetic RNA. The mRNA undergoes translation to form viral proteins which are assembled accompanied by genetic RNA in form of virion. These newly formed virions are released from host cells by rapturing plasma membranes and got matured by the help of protease enzyme Kirchhoff, Numerous bioactive metabolites have been tested and reported for having efficacy to block the steps of multiplications of this virus Figure 2. Researchers demonstrated that interaction of gp of HIV and CD4 receptor of host cell surface has been inhibited by EGCG and ajoene Williamson et al. Reverse transcription is one of the major molecular targets of discovery of antiviral drugs against HIV. Bangladeshi medicinal plant-derived biomolecules anolignan-A, anolignan-B, ajoene, and EGCG inhibited this step by inhibiting RT enzyme. EGCG inhibits this step by interfering Nrf2, AKT, and AMPK signaling transduction pathways which are essential for regulation of viral replication. Li et al. Besides, this biomolecule affects uncoating and nuclear translocation of genetic materials indirectly by downregulation of the expression of p24 gene Xu et al. Synthesized viral proteins are essential components for formation of new virions. Curcumin, found in Curcuma longa , has been reported for degradation of newly synthesized viral proteins Jennings and Parks, Maturation of newly released virions is mandatory for attaining infectivity which involves protease enzyme-regulated proteolytic cleavage. This protease enzyme is inhibited by oleanolic acid Tshilanda et al. FIGURE 2. Impact of bioactive metabolites derived from Bangladeshi medicinal plants on molecular targets of various steps of multiplication process of HIV. RT, reverse transcriptase; EGCG, epigallocatechingallate; and gp, glycoprotein HBV is a unique type of virus that attacks the hepatocytes resulting severe liver infection. Its genomic material is partially double-stranded DNA, commonly known as relaxed-circular DNA or rcDNA. The multiplication process of this virus is distinctive which involves complex and sequential stages Grimm et al. The genomic rcDNA gets translocated to nucleus where host proteins and enzymes repair it by covalent ligation of DNA double strands and form complementary closed circular DNA or ccDNA. It is a highly stable molecular template that exhibits capability to modulate the progression status of severe and barely curable chronic liver infection. After that, the transcription of ccDNA generates subgenomic RNA sgRNA and pre-genomic RNA pgRNA. Bioactive molecules, such as EGCG and curcumin have been reported to inhibit this transcription step leading to reduction of viral load Xu et al. FIGURE 3. Impact of bioactive metabolites derived from Bangladeshi medicinal plants on molecular targets of HBV. This multiplication cycle proceeds by translation and processing of viral antigen particles from sgRNA. Hepatitis-B surface antigen HbsAg and hepatitis-B e antigen HbeAg are predominantly used screening parameter to assay anti-HBV activity. HbsAg is essential for viral assembly whereas HbeAg is a circulating protein in blood of infected patients during active replication stage. This HbeAg level is an indicator of predicting that the patient is whether infectious to others or not Grimm et al. Besides, EGCG diminished the expression of these antigens significantly Xu et al. Alternatively, the pgRNA undergoes encapsidation followed by a complex process of reverse transcription to form single strand - DNA or ssDNA. This step was inhibited by EGCG and kaempferol in various investigations Xu et al. Plant metabolites possess multiple therapeutic activities. They can produce synergistic effects resulting superior therapeutic outcomes. Along with numerous advantages, a number of challenges must be overcome during drug discovery process. The major hindrance is drugability of the plant metabolites. Pharmacokinetic ADME absorption, distribution, metabolism and elimination parameters are the crucial factors that affect the drugability of a plant-derived compound. Fortunately, advancement of novel drug delivery systems and nanotechnologies enlighten the hope of developing plant metabolites as potential drugs. Already a number of plant metabolites have been formulated as novel drug delivery systems Table 5. Other impending challenges are a procurement and authentication of plant materials; b application of high-throughput screening bioassays and scale-up of bioactive lead compounds; and c complexity in isolation and purification processes Jachak and Saklani, Moreover, the toxicities of plant metabolites are sometimes overlooked during laboratory based assays which are observed during clinical trials. Isolation, purification, and bioassay of pure plant-derived compounds are relatively complex, time consuming and required so much efforts, thus failure of drug development at clinical trial phases are very disappointing Phu et al. TABLE 5. Effective delivery systems for oral delivery of plant metabolites with antiviral activity Ben-Shabat et al. In this review, we have summarized the overview of 46 antiviral medicinal plants from 25 families cultivated and originated in Bangladesh. Moreover, bioactive phytochemicals are not profiled for all of these plants. From the available data regarding these plants, a total of 79 compounds with antiviral activities have been found. Amongst them, about 37 bioactive compounds have significant antiviral activities accompanied by mechanistic explanation. These compounds showed potential inhibitory activities against SARS-CoV-2, HIV, HBV, HCV, HSV, DENV, influenza virus and so others. EGCG, oleanolic acid, hesperidin, quercetin, curcumin, kaempferol, and andrographolide showed activity against multiple viruses. Adequate studies are not available regarding structure activity relationship of these bioactive compounds which are crucial to develop drugs active against fatal viruses. Thus, for the development of desired antiviral drug molecules from these medicinal plants, further investigations should be necessary to unveil the mechanism of antiviral activities of the isolated bioactive metabolites along with enlightenment of the structure activity relationship. SB: Generated the idea and contributed to writing the manuscript followed by editing; KM, AA, and RB: Contributed to writing the most important sections of the manuscript including the drawing of the figures; MA: Contributed to the dissemination of ideas on viral diseases and selection of Bangladeshi herbal plants to be used with evidence for writing the manuscript. He also played a vital role in editing the manuscript. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Abd El-Wahab, A. In Vitro study of the Antiviral Activity of Zingiber Officinale. Planta Med. CrossRef Full Text Google Scholar. Al Rawi, A. Antiviral Activity of Mangifera Extract on Influenza Virus Cultivated in Different Cell Cultures. Pure Appl. Fennel is a licorice-flavored plant that may fight certain viruses. A test-tube study showed that fennel extract exhibited strong antiviral effects against herpes viruses and parainfluenza type-3 PI-3 , which causes respiratory infections in cattle According to animal research, fennel may also boost your immune system and decrease inflammation , which may likewise help combat viral infections Garlic is a popular natural remedy for a wide array of conditions, including viral infections. In a study in 23 adults with warts caused by human papillomavirus HPV , applying garlic extract to affected areas twice daily eliminated the warts in all of them after 1—2 weeks 16 , Additionally, older test-tube studies note that garlic may have antiviral activity against influenza A and B, HIV, HSV-1, viral pneumonia, and rhinovirus, which causes the common cold. However, current research is lacking Animal and test-tube studies indicate that garlic enhances immune system response by stimulating protective immune cells, which may safeguard against viral infections Lemon balm extract is a concentrated source of potent essential oils and plant compounds that have antiviral activity Test-tube research has shown that it has antiviral effects against avian influenza bird flu , herpes viruses, HIV-1, and enterovirus 71, which can cause severe infections in infants and children 8 , 20 , 21 , 22 , Peppermint is known to have powerful antiviral qualities and commonly added to teas, extracts, and tinctures meant to naturally treat viral infections. Its leaves and essential oils contain active components, including menthol and rosmarinic acid, which have antiviral and anti-inflammatory activity In a test-tube study, peppermint-leaf extract exhibited potent antiviral activity against respiratory syncytial virus RSV and significantly decreased levels of inflammatory compounds Rosemary is frequently used in cooking but likewise has therapeutic applications due to its numerous plant compounds, including oleanolic acid Oleanolic acid has displayed antiviral activity against herpes viruses, HIV, influenza , and hepatitis in animal and test-tube studies Plus, rosemary extract has demonstrated antiviral effects against herpes viruses and hepatitis A, which affects the liver 28 , Echinacea is one of the most popularly used ingredients in herbal medicine due to its impressive health-promoting properties. Many parts of the plant, including its flowers, leaves, and roots, are used for natural remedies. In fact, Echinacea purpurea , a variety that produces cone-shaped flowers , was used by Native Americans to treat a wide array of conditions, including viral infections Several test-tube studies suggest that certain varieties of echinacea , including E. pallida , E. angustifolia , and E. purpurea , are particularly effective at fighting viral infections like herpes and influenza Notably, E. purpurea is thought to have immune-boosting effects as well, making it particularly useful for treating viral infections Sambucus is a family of plants also called elder. Elderberries are made into a variety of products, such as elixirs and pills, that are used to naturally treat viral infections like the flu and common cold. A study in mice determined that concentrated elderberry juice suppressed influenza virus replication and stimulated immune system response Licorice has been used in traditional Chinese medicine and other natural practices for centuries. Glycyrrhizin, liquiritigenin, and glabridin are just some of the active substances in licorice that have powerful antiviral properties Test-tube studies demonstrate that licorice root extract is effective against HIV, RSV, herpes viruses, and severe acute respiratory syndrome-related coronavirus SARS-CoV , which causes a serious type of pneumonia 35 , 36 , Astragalus is a flowering herb popular in traditional Chinese medicine. It boasts Astragalus polysaccharide APS , which has significant immune-enhancing and antiviral qualities Test-tube and animal studies show that astragalus combats herpes viruses, hepatitis C, and avian influenza H9 virus 39 , 40 , 41 , Lactoferrin is an iron-binding glycoprotein, which has exhibited antiviral activity against a wide range of human and animal viruses both DNA and RNA , including hepatitis C HCV through the direct binding of the peptide to the HCV particles , HSV through inhibition of virus-host interactions, or through inhibition of human immunodeficiency virus HIV replication in host cell. To other reported lactoferrin-affected viruses belong poliovirus , calicivirus , rotavirus and SARS coronavirus Lactoferrin prevents entry of virus in the host cell and its antiviral mechanisms vary among viruses, where it may bind either directly to the virus particle or to the host cell receptor or coreceptor , , Hepcidin, a amino-acid antimicrobial peptide LEAP-1 , is predominately expressed by liver hepatocytes and is the principal regulator of iron absorption The effects of hepcidin on the pathogenesis of viral infections is not well understood; however, expression of hepcidin has been reported following a number of human and murine viral infections It was postulated that hepcidin expression may be upregulated at later stages of infection when iron levels are elevated. Increased hepcidin levels in HIV-1 positive plasma donors of both acute as well as transitioning to chronic infections were reported. HIV replication is iron-dependent and the hepcidin-induced sequestering of iron in cells such as lymphocytes and macrophages is a highly favourable condition for HIV pathogensis Rajanbabu et al. The presence of TH decreased the number of plaques formed by the cytopathic effect of IPNV in the CHSE cells. In addition, the presence of hepcidine showed, further, modulation of interleukin, annexin and other viral-responsive gene expressions and, hence, demonstrated immunomodulatory functions. There is a requirement to improve the delivery and stability of these peptides whilst retaining their functionality and a few strategies have been proposed. As an example, in the study by Zhang et al. In vitro antiviral activity of this nanoformulation against both HCV and HIV were retained. In vivo incorporation was also able to decrease the viral load in mice transplanted with human lymphocytes and HIVinfected A subsequent study of using the same nanoformulation in a galactosylated form, was tested as liver-specific delivery system. It exhibited prominent advantages to prevent HCV association with lipid droplets and was able to suppress the intracellular expression of HCV proteins in an in vitro assessment. In addition, in vivo assessment indicated preferential accumulation in the liver of the tested animals. Another strategy to prevent protease degradation is to substitute L amino acids with D-amino acids. Jackman et al. The peptide showed promise in tackling Zika virus-infected mice, reducing viral load and inflammation in the brain. Subsequent study by Camargoes et al. Graphene is a two-dimensional layer of sp 2 -hybridised carbon atoms, arranged in a hexagonal lattice, that has demonstrated extraordinary properties, such as high electrical and thermal conductivity It is being used in commercial products, like nanocomposites and electronics. This latter nanoscale particulate material can also be functionalised with different surface chemistries, leading to derivatives such as graphene oxide GO and reduced graphene oxide rGO , which have varying amounts of oxygen-containing functional groups attached to the basal plane GO has been shown to act as an antiviral agent, suppressing the infection of several different viruses, including pseudorabies, tomato bushy stunt virus, respiratory syncytial virus and HSV , , , The structure of the flakes, with their high surface-to-volume ratios and sharp edges, has proved destructive to viruses and their inherent negative charge has been attributed to the observed virucidal properties , , , In some cases, GO has been used in partnership with other known antiviral materials such as silver nanoparticles or sulfonated magnetic nanoparticles to achieve antiviral activity Easy chemical modification of GO and rGO with different functional groups that are already understood to have a detrimental effect on viruses, such as polyglycerol sulfate and beta-cyclodextrin, allows further improvement in antiviral properties. While electrostatic interactions between polyglycerol sulfate and virus particles trigger the binding of graphene to viruses, preventing viral adhesion to the host cell, alkyl chains induce a high antiviral activity by secondary hydrophobic interactions However, these effects on viruses have only been demonstrated for GO flakes when used in assays, rather than on surfaces. Graphene has been shown to have antimicrobial properties, with the reduction in Escherichia coli E. coli proven in different studies The physical interaction of different graphene derivatives graphite, graphite oxide, rGO and GO is understood to affect the cellular membrane integrity, metabolic processes and morphology of microorganisms However, it has also been demonstrated that different types of carbon-based 2D materials can have different effects on E. coli , with some surfaces actually promoting the proliferation of the bacterium and the formation of a dense biofilms This confirms the issue that a lack of material characterisation can lead to very different performance of graphene-enhanced surfaces than expected. At the same time, commercially available face masks have now entered the market that are antibacterial and contain nanoscale graphitic flakes. At the same time, these length scales were found to be harmless to larger mammalian cells. In contrast, a CVD graphene layer grown horizontally on the surface did not show the same antimicrobial properties. However, this is a rapidly developing field and CVD-grown graphene typically uses a copper catalyst surface for growth, with high coverage of single-layer graphene on a copper surface already achievable in industrial-scale, roll-to-roll processes , Graphene may therefore be a complementary addition to already successful copper surfaces, or polymers to enhance their antiviral properties. Composites offer an attractive strategy in fabricating useful materials with antiviral properties. Combining different classes of materials or incorporating antiviral moieties, e. Silver nanoparticles AgNPs are known for their excellent antiviral properties. However, differently to silver in its metal bulk form, using free AgNPs, due to their size and properties, poses several drawbacks such as particle aggregation, cytotoxicity or genotoxic damage by inhalation or ingestion into human body in larger quantities. Park et al. They suggested that the major antiviral mechanism of this material was its interaction with the components present on the viral membrane. Martinez-Abad et al. studied the incorporation of 0. The PLA-silver films showed antibacterial and antiviral activity in vitro, with increasing effects at higher silver concentrations when tested against Salmonella and feline calicivirus. Mori et al. The antiviral activity was evaluated from the decreased TCID 50 ratio of viral suspensions between composite-treated samples and controls. Composites with different sizes of AgNPs were tested and stronger antiviral activity was observed for smaller particles for comparable concentrations of incorporated AgNPs. For all the tested particle sizes, the antiviral activity increased with increasing concentration of the particles in the composite. In another study with AgNPs composite , chitin nanofibers sheets CNFSs with immobilized AgNPs also showed antiviral efficacy against H1N1 influenza A virus. Tyo et al. The composites were fabricated from polycaprolactone PCL fibres surrounding polyethylene oxide PEO fibres that incorporated methoxy poly ethylene glycol -b-poly lactide-co-glycolide mPEG-PLGA GRFT NPs. The efficacy of GRFT NP-EFs was assessed using human immunodeficiency virus HIV-1 pseudovirus assays, demonstrating complete in vitro protection against HIV-1 infection. Monmaturapoj et al. They speculated this composite as a promising material for use in antimicrobial filtration materials in e. medical face masks. In another study with titanium dioxide, Amirkhanov et al. In a study by Grover et al. Even though the test lacked testing on a broad virus spectrum, it shows the potential of perhydrolase acyl donor substrates, such as propylene glycol diacetate PGD , glyceryl triacetate or ethyl acetate, to engineer antiviral materials with potential use in antiviral paints in hospital to reduce the propagation of infection. In Table 3 , we provide a summary of materials with antiviral properties with, where reported, the mechanisms of action and persistence. Antiviral materials and coatings have very broad applications, from antiviral food packaging and food contact surfaces for controlling human enteric viruses , to health products for prevention of sexually transmitted infections to PPE in the healthcare sector. The applications dictate the different properties of materials. For example, in food production and retail, the antiviral materials cannot be toxic Materials used in public transport need to be stable, durable and non-flammable. Here, we give an overview of practical applications of antiviral materials and coatings which are summarised in Table 4. Example applications in the context of a hospital setting are illustrated in Fig. Four classes of surfaces are shown; a hard surfaces such as touch screens and door handles, b large area and infrastructure such as walls, floors and tables; c soft surfaces including textiles and ambulance interior and d PPE including masks, gloves, visors and coverings. PPE is clearly a prime area of importance, to protect people from the risk of contact infection. As PPE includes facial masks or visors, protective suits, spill gowns, gloves, boot covers, goggles. etc, it requires compatibility with a wide range of materials from woven fabrics, used in masks, to disposable aprons. However, generally the materials should be non-toxic and skin friendly. Masks and respirators are one of main application of antiviral materials since the primary transmission carriers for respiratory viruses are droplets and aerosols, which are released through a cough, sneeze or when speaking and even breathing. During the SARS-CoV-2 pandemic, face masks and respirators are often mandated in public areas to limit the spread of infections The conventional type of face masks and respirators composed of woven or non-woven fabric block the virus by filtration of aerosols and droplets. However, the virus persists on the surface 40 , which leads to a risk due to incorrect wearing of masks or their reuse. Research has focused on developing self-cleaning masks by using different materials and technologies , especially nano-based materials and techniques, some of which are already available or close to the market. One popular strategy is incorporating antiviral nanoparticles into fibrous membranes of the mask or depositing an ultrathin nanoparticle layer on the respirators. Examples include copper oxide and silver nanoparticles incorporated into nanofiber membranes or the fabric of masks , Another way is to make masks superhydrophobic, so that virus-laden droplets would not be able to remain on the masks. A possible approach is depositing a few layers of graphene onto commercial surgical masks Other super-hydrophobic materials, such as fluorinated polymers and metallic nanowires, have also the potential to be used in respiratory masks Antiviral compounds incorporated to other types of PPE, such as apron or gloves, would further reduce the risk of infection for health care workers. Many antiviral materials, already used in masks and respirators, e. Some drawbacks of utilising metal ions or metallic nanoparticles in PPE or other everyday-use surfaces should be considered when designing, manufacturing and implementing the products. Firstly, ion leaching can occur leading, eventually, to the loss of antiviral and antimicrobial properties of the material , Secondly, there is a potential risk to the environment that metallic nanoparticles can exert after being released from products with, for example, domestic or industrial wastewater , By incorporating daylight-active chemicals into rechargeable nanofibrous membranes RNMs , photoactive RNMs could act by releasing ROS to provide biocidal functions under dim light or dark conditions and store the biocidal activity under light irradiation, which could be potentially incorporated as a surface protective layer of PPE. There have been many advances to improve the antibacterial properties of medical devices especially those that go into the wet or humid environment of the body e. catheters, tracheal and laryngeal tubes. Biopolymers and biocompatible polymer coatings could also be used to reduce viral transmission. Another application of antiviral materials is the use of antiviral surfaces or surface coatings in public settings such as healthcare facilities or public transport system, to slow down the spread of virus through fomites. This application requires durable materials with long-term weeks or even months antiviral efficiency. Similar to PPE, metal ions such as silver and copper are popular candidates for use in public areas. Deposition of silver clusters, through the photoreduction of a silver salt, directly on the surface could be implemented, e. The coatings based on polymers, incorporating metallic nanoparticles or metal ions, could protect the metal from oxidation and corrosion and could also be engineered for slow release of metal ions, providing long-lasting antiviral properties. A non-release approach, enhancing the durability of antiviral coatings, was proposed by Haldar et al. Some of the materials discussed in this review can be applied as a paint and these could be applied to a wide variety of surfaces from walls, doors and cabinets to equipment and other hard surfaces. The ubiquitous touch screen is found everywhere, from personal mobile phones to medical equipment, and is notorious for harbouring bacteria and viruses. Many of the materials, such as copper, discussed in this review could be potentially used in thin-film coatings on glass surfaces. Door handles, taps and other frequently touched hard surfaces could similarly benefit from metal coatings such as copper. An alternative way is to generate nanostructured topography on industrially relevant surfaces that can physically inactivate viruses. Recently, Hasan et al. With excellent durability, this strategy could be potentially used in hospitals and other public areas. The aim of this review is to provide an overview and better understanding of the current state of knowledge, research direction and practices in the area of antiviral materials and coatings. We focus on the reported mechanisms of action. The repertoire of materials with antiviral and antimicrobial properties is large and varied. Adding to that further possibilities of design and engineering of new chemistries, provides many options. Antimicrobial properties of these materials are widely studied but reports on antiviral properties are much fewer and this is a gap that should be considered. As can be seen, there is a significant resource of existing literature on viral persistence on different surfaces. However, a quantitative or even semi-quantitative analysis of the data is hampered by a lack of equivalence in the ways that persistence is measured or a consistent set of virus classes that are used to challenge the materials. There are existing ISO, ASTM, US Federal and EU standards on the measurement of antiviral activity but a lack of use in the literature. The most frequently used method is the end point dilution assay TCID 50 , though as noted earlier, the results are often difficult to interpret and are subjective. There appears to be a compelling need for systematic studies of different material types, challenged with specific virus strains of representative classes enveloped, non-enveloped etc. using quantitative approaches. Furthermore, a reference standard surface, that could be used in an intercomparison study, would greatly benefit the community by providing a base-line of repeatability within a lab and replicability between laboratories. We believe that such studies would considerably increase the value and re-use of data created in future studies. Copper is one of the most effective and simplest of the materials in this review and would appear to be easily integrated, e. Touch-screen displays could have thin films containing copper. However, increased exposure to copper would need careful consideration in terms of other health effects. Indeed, unwanted environmental effects caused by leaching may be one of the most significant issues to be considered in the deployment of antiviral surfaces. Natural products may provide the right balance of antiviral efficacy and environmental impact. It is clear that material science can play a very important role in the development of conceptual and practical measures to slow infectious outbreaks. Both existing and innovative broad-spectrum antiviral strategies should be considered, which could contribute to the challenge and preparedness of future viral pandemics. Walker, P. et al. 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| Antiviral drug - Wikipedia | Two antiviral bioactive compounds properfies been isolated from ethanolic extract Antiviral virus-fighting properties virrus-fighting whole plant namely maltol b-D-apiofuranosyl-b-D-glucopyranoside, Sleep hygiene grevilloside G. Biomedicines 6, The IC 50 for LF1 were 0. In Overview of Reverse TranscriptionEds Coffin, J. Two active ingredients that household cleaning products commonly include are sodium hypochlorite and hydrogen peroxide. Costa, F. |
| Antiviral surfaces and coatings and their mechanisms of action | Communications Materials | Virus-fightint mechanisms through Antivirl EOs vkrus-fighting antiviral actions prolerties, direct actions on Sleep hygiene viruses, pfoperties Sleep hygiene steps involved Hydration for staying hydrated during illness virus attachment, penetration, Microbe-repellent materials replication, and release from host cells and inhibition of vital viral enzymes Ma and Yao ; Schnitzler et al. Vaccine development is actively being researched, but it may take over a year to become available to general public. This herb produces curcumin which possesses diverse pharmacological activities. purpureaare particularly effective at fighting viral infections like herpes and influenza This protein has shown promise in slowing down the progression of HIV to AIDS About this article. |
Antiviral virus-fighting properties -
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Intens Care Med — Download references. Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan. Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan.
Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan. Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden Penang, Malaysia.
You can also search for this author in PubMed Google Scholar. Correspondence to Muhammad Asif. This review is purely for academic purposes. The authors declare no conflict of interest in the current work. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Introduction The severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 has emerged as a new respiratory pathogen and is responsible for large-scale morbidities and mortalities around the globe.
Search methodology Selection criteria for studies The current review provides precise and comprehensive information on the essential oils and their possible contribution in the prevention and treatment of COVID Results and discussion Enveloped viruses are known to respond sensitively to essential oils Schnitzler et al.
Eucalyptus oil Essential oils obtained from eucalyptus Eucalyptus globulus are traditionally used to treat various respiratory ailments including pharyngitis, bronchitis, and sinusitis. Garlic oil Garlic has been used as a medication to treat common cold, influenza, and other kinds of infections for centuries.
Anethole, cinnamaldehyde, carvacrol, geraniol, cinnamyl acetate, Lterpineol, thymol, and pulegone An in silico study conducted by Kulkarni and colleagues evaluated the efficacy of a variety of EOs present in diverse plant families to block the S1 also called receptor binding domain, RBD subunit of spike S proteins of SARC-CoV Eugenol, menthol, and carvacrol Silva and colleagues used molecular docking techniques to screen the anti-SARC-CoV-2 efficacies of eugenol, menthol, and carvacrol, major components of EOs, against various proteins targets of SARC-CoV Full size image.
Conclusion and future recommendations COVID has emerged as a very serious threat to global health. References Barboza JN, da Silva Maia Bezerra Filho C, Silva RO, Medeiros JVR, de Sousa DP An overview on the anti-inflammatory potential and antioxidant profile of eugenol.
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abb Article CAS PubMed PubMed Central Google Scholar Gibbs JEM Essential oils, asthma, thunderstorms, and plant gases: a prospective study of respiratory response to ambient biogenic volatile organic compounds BVOCs. J Asthma Allergy — Article CAS Google Scholar Girija ASS, Shankar EM, Larsson M Could SARS-CoVinduced hyperinflammation magnify the severity of coronavirus disease CoViD leading to acute respiratory distress syndrome?
Int J Med Lab — CAS Google Scholar Kulkarni SA, Nagarajan SK, Ramesh V, Palaniyandi V, Selvam SP, Madhavan T Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein.
Molecules Article CAS Google Scholar McCord JM, Hybertson BM, Cota-Gomez A, Gao B Nrf2 activator PB ® as a potential therapeutic agent against COVID Altern Med Rev J Clin Ther —47 Google Scholar Schnitzler P, Schuhmacher A, Astani A, Reichling J Melissa officinalis oil affects infectivity of enveloped herpesviruses.
ch10 Article Google Scholar Sharma AD, Kaur I a Jensenone from eucalyptus essential oil as a potential inhibitor of COVID 19 corona virus infection. Res Rev Biotech Biosci —66 Google Scholar Sharma AD, Kaur I b Eucalyptol 1,8 cineole from eucalyptus essential oil a potential inhibitor of COVID 19 corona virus infection by molecular docking studies.
Preprints: Shuai C et al An overall picture of SARS coronavirus SARS-CoV genome-encoded major proteins: structures, functions and drug development. Cureus e PubMed PubMed Central Google Scholar Vimalanathan S, Hudson J Anti-influenza virus activity of essential oils and vapors.
Am J Essent Oils Nat Prod —53 Google Scholar Wang M et al Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus nCoV in vitro.
Diversity Article CAS Google Scholar Yang Y et al The deadly coronaviruses: the SARS pandemic and the novel coronavirus epidemic in China. Funding This research received no external funding. View author publications. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions Reprints and permissions. Lee et al. The naviculan is a heteropolysaccharide consisting of fucose, xylose, galactose, mannose, rhamnose, and sulfate with an average MW of ~2.
It is a broad-spectrum antiviral against HSV-1, HSV-2, and influenza A virus with IC 50 of 14, 7. Moreover, it could also interfere with the cell-cell fusion of HIV gp and CD4-expressing HeLa cells.
Therefore, it might prevent HIV infections. Bacteria including cyanobacteria or blue-green algae have the ability to synthesize polysaccharides for various purposes such as storage, cell protection, and adhesion. Polysaccharides accumulated in cells are called intracellular polysaccharides ICP.
While those outside of cell are called extracellular polysaccharides or EPS. The latter are secreted by cells or produced extracellularly using cell wall-anchored enzymes Bacterial polysaccharides show biological bioactive activities, including anti-inflammatory, anticancer, antimicrobial, antioxidant, and immunomodulatory 91 — They showed an inhibitory effect against various viruses, both DNA and RNA viruses.
For example, Arthrospira platensis formerly Spirulina platensis produced calcium spirulan, a sulfated polysaccharide, with antiviral activity against several enveloped viruses.
The calcium spirulan composed of rhamnose, ribose, mannose, fructose, galactose, xylose, glucose, glucuronic acid, galacturonic acid, sulfate, and calcium. This polysaccharide showed antiviral activity against HSV-1, human cytomegalovirus HCMV , measles, mumps, influenza A, and HIV-1 viruses by inhibiting virus penetration Spirulan-like substances extracted from A.
platensis showed strong antiviral activity against HCMV, HSV-1, human herpesvirus type 6 HHV-6 , and HIV Their mechanisms depended on the type of virus. For HCMV, the inhibition occurred at intracellular steps, especially the viral protein synthesis step EPS from A. platensis also inhibited koi herpesviruses KHV.
Reichert et al. The virus infections were blocked when nostoflan was added at the same time as viral infections. Therefore, nostoflan blocked the viruses at the virus adsorption stage.
The IC 50 values of nostoflan for HSV-1, HSV-2, HCMV, and influenza A viruses were 0. EPS26a from Lactobacillus sp. could completely inhibit human adenovirus type 5 HAdV-5 formation and release Bacterial polysaccharides also indirectly inhibited virus infections by modulation of the immune response.
For instance, an EPS produced by Lactobacillus delbrueckii OLLR-1 activated the Toll-like receptor 3 TLR3 and the expression of interferon IFN -α, IFN-β, MxA, and RNase L in porcine intestinal epithelial PIE cells, which was associated with the innate antiviral immune response Mizuno et al.
Antiviral bacterial polysaccharides are also shown in Table 1. Fungi are unicellular-to-multicellular eukaryotic microorganisms. They can produce a plethora of biologically active compounds, especially secondary metabolites. Similar to algae and bacteria, fungal polysaccharides primary metabolites also showed antiviral activity.
Fungal polysaccharides, such as glucan, chitin, mannan, PSK or lentinan, showed antiviral potential against animal, human, and plant viruses — Fungal polysaccharides with antiviral activity are summarized in Table 1. Porodaedalea pini formerly known as Phellinus pini produced two antiviral polysaccharides EP-AV1 and EP-AV2 against HSV-1 and coxsackie virus B3 CVB3 in Vero and HeLa cells, respectively.
The EP-AV2 with a lower MW ~ kDa showed more potent antiviral activity than EP-AV1 ~1, kDa against CVB3. These polysaccharides specifically inhibited HSV-1 more than CVB3 as indicated by their EC 50 values. The EC 50 values of EP-AV1 and EP-AV2 for HSV-1 were 0.
Furthermore, a polysaccharide extracted from the mycelium and fruiting body of Lentides edodes was able to inhibit poliovirus type 1 PV-1 and bovine herpes virus type 1 BoHV-1 with IC 50 values of 0.
In another study, Grifola frondosa mycelia were evaluated as a source of antiviral polysaccharides, observing that it had the antiviral polysaccharide, GFP1.
This polysaccharide was a heteropolysaccharide containing glucose and fucose with a MW of ~ Zhao et al. The GFP1 suppressed the viral protein expression and viral RNA genome synthesis.
Fungal polysaccharides also showed important antiviral properties against animal viruses. For example, a polysaccharide from L. edodes , called lentinan comprised of glucose, mannose, and galactose with MW of ~3. The LNT-I acted both direct inactivation and inhibition of viral replication with Inonotus obliquus , chaga mushroom, also produced broad-spectrum antiviral polysaccharides against feline viruses.
The polysaccharides suppressed infections of feline calicivirus FCV , feline herpesvirus 1 FHV-1 , feline panleukopenia FPV , feline coronavirus FCoV , and feline influenza FIV, H3N2, and H5N6 viruses. Therefore, polysaccharides from different species show various biological activities with different levels of action.
Sulfated polysaccharides derived from marine microalgae and seaweeds showed many different bioactive properties and were effective against viruses at low concentrations, compared to other polysaccharides.
In addition, bacteria and fungi are easily grow on simple media or agricultural wastes. The production can be done using controllable conditions and they produce high amounts of polysaccharides.
Therefore, it would also benificial if the bioactivities and physicochemical properties of bacterial and fungal polysaccharides could be modified.
The molecular modification of polysaccharides is an alternative approach to modulate their properties. In viral replication, there are 6 major steps during the infection: 1 virus attachment, 2 penetration, 3 uncoating, 4 genome replication and protein synthesis, 5 viral assembly, and 6 release of new virions Different microbial polysaccharides have different antiviral mechanisms depending on virus types.
The polysaccharides mostly prevented the initial steps of the virus life cycle. However, some microbial polysaccharides could inhibit viral replication and protein translation. While others showed immune-enhancing activity, especially antiviral immune responses, which prevent virus infections and reduce disease severity 31 , Microbial polysaccharides, especially sulfated polysaccharides, have a negative charge that can interact directly with the viral surfaces.
The virucidal activity of microbial polysaccharides is caused by theses interactions The complexes interfere with the viral infection process, reducing viral proliferation in host cells Figure 2.
For example, polysaccharides extracted from Auricularia auricular , a basidiomycete mushroom, can inhibit NDV in CEF cells. During the process of adding polysaccharides and virus simultaneously, the virus inhibitory rates were higher than pre- and post-addition of the polysaccharides.
These polysaccharides might be combined with virus particles to block virus attachment to host cells Inonotus obliquus polysaccharides also directly blocked feline virus virions FCV, FHV-1, FPV, feline coronavirus FCoV, and FIV.
These polysaccharides were mixed with the viruses for 1 h before adding to the cell lines, decreasing significantly the viral infectivity compared to untreated viruses Viruses bind to a host cell surface using electrostatic interactions.
Some microbial polysaccharides mimic virus particles. Microbial polysaccharides, especially sulfated polysaccharides, are strongly anionic and bind to the positively charged host cell receptors blocking virus attachment, which prevents virus infection Figure 3 7.
Figure 3. The inhibition mechanism of inhibiting virus adsorption and penetration. Many microbial polysaccharides act at this step. For example, a polysaccharide SP-2a from S.
Human influenza virus H was blocked by sulfated polysaccharides from Gracilaria lemaneiformis , a red alga, at virus adsorption and replication on host cells. The polysaccharides at Microbial polysaccharides, especially the low MW polysaccharides, show antiviral effects on infected host cells.
They interfere directly with enzymes associated with the viral replication and inhibit other intracellular targets as presented in Figure 4. Carrageenans are sulfated polysaccharide that are available from most of red seaweeds.
These polysaccharides show a broad-spectrum antiviral activity. González et al. When carrageenan was added 1 h after HSV-1 infection, viral proteins were not detected, whereas when carrageenan was added immediately, viral proteins were detected.
Furthermore, polysaccharide GFP1 from G. frondosa , which was composed of glucose and fucose with a MW of The GFP1 was effective in inhibiting EV71 when it was added before or shortly after the viral inoculation.
The viral RNA synthesis and VP1 protein were suppressed in a dose-dependent manner Figure 4. The inhibition mechanism by interfering with viral genome replication and protein synthesis. During virus infection in animals, the body induces the immune responses to defend against viral infection.
The responses regulate immune cells such as natural killer NK cells and macrophages, and increase the production of cytokines, i. The microbial polysaccharides interact with cell receptors on the macrophage and NK cell, and then activate the cells using the nuclear factor kappa B NF-κB and the mitogen-activated protein kinase MAPK signaling pathways.
These proteins are inducible factors, which increases the gene expression of various cytokines, chemokines, enzymes, and other proteins involving both innate and adaptive immunity The IFN secreted from activated immune cells triggers activation of other immune cells including NK cells, macrophages, and T-cell lymphocytes, which have important roles in the host immune system and antiviral responses.
Meanwhile, microbial polysaccharides can activate NK cells that non-specifically kill virus-infected cells by secreting perforins and granzymes Figure 5.
Figure 5. The modulation of the antiviral immune response by activation of macrophage and NK cell using the NF-κB and MAPK signaling pathways. Several polysaccharides can enhance the antiviral immune responses, thus reducing the number of virus particles and the severity of diseases.
For example, an EPS extracted from S. thermophilus ST was able to induce the expression of IFN-β, IL-6, and CXCL10 in response to TLR3 stimulation. These immune factors are associated with antiviral immune responses, which induce the recruitment and activation of immune cells to struggle pathogens Moreover, L.
delbrueckii OLLR-1 produced immunomodulatory EPS. These EPS activated TLR3 and induced the expression of IFN-α, IFN-β, MxA, and RNase L. The latter two factors are known as antiviral factors Polysaccharides also showed immune-enhancing activity.
Ren et al. edodes mycelia could modulate the immune response by up-regulating the expression of IFN-1 and IFN-γ to prevent IHNV infection. In addition, an acidic polysaccharide APS from Cordyceps militaris enhanced TNF-α, IFN-γ, and nitric oxide NO production, and induced the expression of several cytokines: IL-1β, IL-6, IL, and TNF-α.
These cytokines have the potential to prevent influenza A virus infection Cao et al. japonica which could increase IFN-α secretion in a dose-dependent manner.
Polysaccharides derived from different sources showed several unique characteristics, properties, and bioactivities at different levels. Their MW, compositions, functional groups, and structural conformations including type of linkage and degree of branching associate with their biological properties, especially antiviral and immunomodulatory activities.
Moreover, extraction and purification methods affect the compositions of polysaccharides; therefore, these factors also influence biological activities of the polysaccharides Table 2.
Some microbial polysaccharides from various sources with different characteristics and bioactivities. Several studies have reported that sulfated polysaccharides could exhibit several biological activities antiviral, anticancer, antioxidant, and immunomodulatory activities , so the sulfate contents could be an important factor affecting antiviral and other bioactivities.
Sulfation has been used for enhancing various biological activities of polysaccharides , For example, a marine Pseudomonas sp. WAK-1 produces extracellular glycosaminoglycan A1 and sulfated polysaccharide A2 with antiviral activity. Matsuda et al. The over-sulfated polysaccharides were called A1S and A2S, respectively.
From the results, over-sulfated polysaccharides A1S and A2S showed higher antiviral activity against influenza A virus than the natural polysaccharides A1 and A2. Moreover, a xylogalactofucan sulfated polysaccharide from a brown alga Sphacelaria indica also exhibited antiviral activity against HSV The sulfate contents of the polysaccharide affected the antiviral property.
Bandyopadhyay et al. The IC 50 values of natural and artificially over-sulfated polysaccharides were 1. Furthermore, Ponce et al. The whole extract A of S. lomentaria was fractionated to yield fractions A0, A5, A10, A20, A30, and A40, with different components, MW, and monosaccharide composition.
A0 was soluble and the fraction A5 was an uronofucoidan. A10—A40 were galactofucans and showed antiviral activity against HSV-1 and HSV-2 with IC 50 values in the range 0. Among the 4 galactofucan fractions, A30 pure galactofucan contained the highest sulfate content A30 showed the strongest antiviral activity against HSV-1 and HSV-2 with IC 50 values of 0.
Therefore, the low content of uronic acids and the high content of sulfate was associated with the antiviral activity of these polysaccharides. In conclusion, sulfate content is an important factor influencing biological activities. Adding sulfate groups into polysaccharide structures led to enhance bioactivities, whereas desulfation decreased their bioactivities.
The MW of polysaccharides also influenced their biological properties. Polysaccharides with low MW could easily pass through target cells to act inside the cells. Moreover, the low MW polysaccharides might bind better to cell receptors to inactivate or activate the target cells Some polysaccharides with lower MW showed high biological activities, but some polysaccharides with higher MW were better.
For example, Surayot et al. In addition, Ponce et al. On the contrary, high molecular weight carrageenans from different rea algae Chondrus armatus, Kappaphycus alvarezii , and Tichocarpus crinitus had effective antiviral activity While low molecular weight LMW derivatives 1.
Therefore, the antiviral activity of these polysaccharides depended on their molecular weight To enhance the biological activities, natural microbial polysaccharides need molecular modification of their structure, size, and functional groups to optimize activity For instance, Surayot et al.
confusa TISTR using HCl and heating in hot water or in a microwave oven. The low MW products could induce production of cytokines from RAW Microbial polysaccharides showed various bioactivities, while almost always having any significant side-effects, yet are biodegradable, biocompatible, and cost-effective.
Microbial and algal polysaccharides may be applied as drug resistance solutions. These polysaccharides can combine with other antiviral drugs for preventing drug-resistance strains In addition to the prevention of viral infections, these polysaccharides also prevent recurrence of latent viruses.
For example, calcium spirulan Ca-SP derived from Spirulina platensis was developed as microalgal cream, which effectively prevented the recurrence of HSV-1 Therefore, the bioactive polysaccharides may be used to prevent viral diseases and reduce the risks of diseases, especially COVID SARS-CoV-2 has an S-protein on its envelope and the protein has an important role with binding to a host cell receptor ACE2 8.
Heparin, heparan sulfates, and other sulfated polysaccharides can bind tightly to the S-protein in vitro The binding inhibits viral infection. Other microbial polysaccharides showed immunomodulatory properties that stimulated the immune system to prevent SARS-CoV-2 infection.
Several microbes can produce sulfated polysaccharides. Beneficial sulfated polysaccharides might be produced from natural microbial polysaccharides Type I IFN, including IFN-α, -β, -ε, -κ, -ω, -δ, -ζ, and -τ, are essential cytokines for antiviral immune responses.
Type I IFN can induce antiviral responses within infected and neighboring cells that block the spread of virus particles. They activate both innate and adaptive immune responses that promote NK cell functions and antibody production , Hadjadj et al.
Many microbial and algal polysaccharides induced type I IFN production in vivo. Thus, these polysaccharides might be applied to modulate the immune system in both patients and healthy people. In severe COVID cases, aggressive inflammatory responses were found and the inflammation caused tissue damage in many organs Some microbial polysaccharides showed anti-inflammatory activity.
These polysaccharides inhibited the production of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8 — ACE2 receptors are expressed by several tissues and organs as described above, especially the respiratory and gastrointestinal tracts.
Microbial polysaccharides with antiviral activity can be used as a nasal spray, metered dose inhaler, or delivered orally to prevent the binding of SARS-CoV-2 Several natural polysaccharides have been designed as nanomaterials for drug delivery systems, such as antiviral agent.
These nanomaterials may be not only used to treat the virus, but also to modulate the immune responses 7. Algal, bacterial, and fungal polysaccharides and sulfated polysaccharides showed pharmaceutical properties due to their biological activities as mentioned above. These polysaccharides could be used as bioactive supplements in foods and could enrich nutritional quality.
Indeed, some of these polysaccharides have been granted as GRAS status by the US FDA, so they can consume to enhance immune response and reduce the severity of viral diseases, especially COVID Some microbial polysaccharides have prebiotic properties, which enhance the proliferation of beneficial intestinal microflora, especially Bifidobacterium spp.
In addition, some algal polysaccharides alginate and laminaran could be fermented by gut microbiota and promoted the growth of Bacteroides, Bifidobacterium , and Lactobacillus species When microbial polysaccharides were consumed, they could enhance the host's immune response and modulate the microbial community microflora.
The microbes degrade the polysaccharides into short-chain fatty acids SCFA such as acetic, propionic, and butyric acids. SCFA show benefit for the maintenance intestinal cells and modulating of the immune system Microbial polysaccharides have the potential to be bioactive ingredients that can be added into foods or food products to enhance the nutritional quality of foods by modulating consumers' immune response.
Therefore, the biological activities of foods supplemented with these polysaccharides should be investigated. Microorganisms produce various types of polysaccharides with unique characteristics and can be produced on a large scale with controllable conditions.
Polysaccharides and sulfated polysaccharides from different microorganism and algae species have different characteristics and levels of bioactivities. Their constituents, structural conformations, MW, and functional groups significantly influence their bioactivities.
To enhance their activities, physical, chemical, or biological modifications might be beneficial. Some sulfated polysaccharides obtained from microbes and algae have been approved as GRAS, which may be used as bioactive ingredients adding in food products to prevent viruses.
Many microbial polysaccharides are safe, biocompatible, biodegradable, and easily available. Therefore, the intake of proper dosage of the right polysaccharides may modulate physiological functions to prevent viral diseases and decrease their damage.
They may be an alternative therapy to treat COVID patients. In the future, the development of polysaccharides as functional food products should be explored.
For foods supplemented with bioactive polysaccharides, more pharmaceutical investigations and clinical evidence are required to analyze their antiviral and immune-enhancing effects.
The mechanisms that occur in the food products against viral infections should also be further investigated. PS, TC, CT, and SY contributed to conception and supervised the project.
WC, NL, KJ, and SS contributed in doing literature searches and wrote the manuscript draft. YP, PR, SW, JR, FB, and PS equally revised and approved the manuscript. All authors have read and approved the final draft manuscript.
The authors gratefully acknowledge the financial support from the National Research Council of Thailand NRCT through the Royal Golden Jubilee Ph. Program, Thailand grant no. Additionally, this work was also partially financially supported along with in-kind support by the Biotechnology Program of the Graduate School of Chiang Mai University; the Cluster of Agro Bio-Circular-Green Industry Agro BCG Faculty of Agro-Industry; and Chiang Mai University.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Dimmock NJ, Easton AJ, Leppard KN. Introduction to Modern Virology. World Health Organization.
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Currently, viral Hydration for staying hydrated during illness is the Hydration for staying hydrated during illness serious virus-fiighting issue which causing unexpected virjs-fighting rate of death Oats for energy. Many viruses are Antuviral yet Sleep hygiene, such as corona virus-2 SARS-CoV-2human immunodeficiency virus HIV virus-tighting, hepatitis Anttiviral, human papilloma virus and so virus-figghting. Furthermore, Antiviral virus-fighting properties toxicities and Advanced fat burning techniques responses to resistant strains of synthetic antiviral drugs have reinforced the search of effective and alternative treatment options, such as plant-derived antiviral drug molecules. Therefore, in the present review, an attempt has been taken to summarize the medicinal plants reported for exhibiting antiviral activities available in Bangladesh along with discussing the mechanistic insights into their bioactive components against three most hazardous viruses, namely SARS-CoV-2, HIV, and HBV. The review covers 46 medicinal plants with antiviral activity from 25 families. Among the reported 79 bioactive compounds having antiviral activities isolated from these plants, about 37 of them have been reported for significant activities against varieties of viruses.
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