Antiviral plant extracts -
Against many viruses, the extracts of Eclipta alba were proved to have strong antiviral activity [ 25 ]. Though the fresh juice of leaves is used for various benefits like increasing appetite, mild bowel regulator, it is mainly used in viruses causing blood borne hepatitis.
It is also used to protect the parenchyma and to promote bile flow which is popularly used to enhance learning and memory. In most parts of the subcontinent, it is used for jaundice, as a deobstruent and cholagogue in hepatic injury and other ailments of liver.
One of the most potent inhibitory activity against HIV-1 integrase [HIV-1 IN] was found in the water extract of Eclipta prostrate [ 26 ]. In Ayurveda, Phyllanthus amarus is an Indian herb that has been used in support liver.
In all tropical regions of the planet, P. amarus is widely distributed. The exact geographic origin of this plant was not found by Paleobotanical studies [ 28 , 29 ]. This plant may be indigenous to the tropical Americas and also to the Philippines or India [ 22 ].
Genus - Phyllanthus. Species - amarus. Binomial name - Phyllanthus amarus. Some of the secondary metabolites that are present in P. amarus include lignins alkaloids, hydrolysable tannins, flavanoids, and polyphenols.
Such phytochemicals and their structure were usually determined by using IR, UV, NMR and mass spectroscopy [ 30 ].
Apart from that, preparative thin layer chromatography and column chromatography are also used by which few new alkaloids were isolated [ 31 ]. Parts of this plant P.
amarus , mostly fresh and occasionally dry are sold and the decoctions are used widely for herbal baths. To treat bladder and kidney disorders, herbal decoction of this plant is used in traditional medicine [ 32 ]. This herb can also be used as tonic and can also be used as an appetizer.
amarus plant extracts is also used as blood purifiers. It also helps to release phlegm for light malaria fevers and anemia [ 33 ]. In combination with many other herbs, this herb is used for curing flu, asthma and fever.
The leaves are boiled and used to treat dysentery and even skin disorders [ 34 ]. For constipation also, studies have proved that extracts are very effective. Apart from that, extracts have even shown anticancer properties.
It also has beneficial effects on liver functions. Several studies in the past have proved that P. amarus inhibits the activity of the HBsAg [ 35 ]. Widespread studies on P. amarus have showed that the extracts possess strong antiviral activities particularly against HBV and HCV.
In Indian system of medicine, a chemo-biological fingerprinting methodology for standardization of P. amarus preparation was even patented [ 36 ].
Evaluation of antiviral activity of Phyllanthus species was evident from aqueous extract showing strong activity against viruses like HSV1 and HSV2 in vero cells by quantitative polymerase chain reaction.
To study protein expressions of treated and untreated infected vero cells, western blot and 2D-gel electrophoresis were most widely used. Phyllanthus amarus along with Phyllanthus urinaria demonstrate the strongest antiviral activity against both HSV1 and HSV2 viruses which is proposed to its action in the early stage of replication and infection [ 37 ].
In conclusion, in the existing scenario, there is an essential need for the development of new antiviral drugs. As on date there are many epidemiological studies that have evaluated different targets of these antivirals and promising results were obtained.
Still a lot of research is needed to find out the actual potential for human use. In comparison to synthetic counterparts, extracts obtained from Boerhavia diffusa , Eclipta alba and Phyllanthus amarus are tend to be safer, very effective and cheap.
The extracts obtained from these plants might have compounds that are true antiviral, but are present at insufficient quantity to inactivate all infectious virus particles. It is very much possible that obtaining active constituents from these plants will be providing many useful leads in the development of effective antiviral agents.
Thus there is an urgent need to find effective antiviral agents as the existing drugs may be effective but in a specific manner. Based on the existing knowledge of traditional medicine, these three plants have to be explored further for formulating effective drugs against various dreadful disease caused by viruses.
Ethnobotanical information Plant Parts used Benefits Information obtained from Reference Boerhavia diffusa Roots In the treatment of piles. Root paste is used to cure bloody dysentery.
It is also used for leukorrhea, rheumatism and stomach ache. The root juice is used in treating asthma, scanty urine and internal inflammation disorders.
India Mitra and Gupta [ 38 ] Eclipta alba Flowers, leaf and roots Remedy for catarrh in infants, toothache, headache and roots are emetic and purgative India Puri [ 39 ] Entire plant Remedy for the treatment of bleeding, hemoptysis, hematuria and itching, hepatitis, diphtheria and diarrhea Taiwan Entire plant As a cooling and restorative herb, which supports the mind, nerves, liver and eyes China Phyllanthus amarus Aerial parts of the plant Used in the treatment of liver, kidney and bladder problems.
Also used for diabetes and intestinal parasites Many parts of the world Chevallier [ 22 ] Entire plant Kidney stones Spain Houghton et al.
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Chapter metrics overview 2, Chapter Downloads View Full Metrics. Impact of this chapter. Abstract Herbal therapy has been an important part of health and wellness for hundreds of years.
Keywords antiviral herbs Boerhavia diffusa Eclipta alba Phyllanthus amarus. Introduction For hundreds of years, herbal therapy has played a major role in maintaining the health and wealth of people around the world.
Taxonomy Kingdom - Plantae Division - Angiospermae Class - Dicotyledoneae Order - Tubiflorae Family - Euphorbiaceae Genus - Phyllanthus Species - amarus Binomial name - Phyllanthus amarus Floral formula Br, Ebrl, p[5], A5 G[3]. References 1.
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Hepatoprotective activity in punarnava: A popular Indian ethnomedicine. Verma HN, Awasthi LP. Occurrence of a highly antiviral agent in plants treated with Boerhaavia diffusa inhibitor. Canadian Journal of Botany. Antiviral activity of Boerhaavia diffusa root extract and physical properties of virus inhibitor.
Awasthi LP, Kluge S, Verma N. Characteristics of antiviral agents induced by Boerhaavia diffusa glycoprotein in host plants. Indian Journal of Virology. Awasthi LP, Menzel G. Effect of root extract from Boerhaavia diffusa containing an antiviral principle upon plaque formation of RNA bacteriophages.
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Natural Product Letters. Houghton PJ, Woldemariam TZ, Shea S, Thyagarajan SP. 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.
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Extdacts access peer-reviewed chapter. Submitted: 18 February Reviewed: 02 May Published: 20 Essential oils for anti-aging com customercare cbspd. Viral Fasting and hormone regulation remain plan challenge Antiviral plant extracts human and veterinary medicine due to extraacts such as viral mutations, new viruses, toxic effects, disease severity, intracellular viability, high costs, and limited availability of antiviral drugs. Despite advancements in immunization and antiviral drugs, there is a need for new and more effective antiviral compounds. Plants produce secondary metabolites that have shown antiviral activity, such as alkaloids, flavonoids, and essential oils. Advanced analytical techniques like HPLC, GC-MS, and NMR spectroscopy are used to identify and characterize these bioactive compounds.
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