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Virology Lectures 2023 #20: AntiviralsStrong anti-viral -
The method is the same as bacteria. Herby, we confirm that all experiments were performed in accordance with relevant guidelines and regulations. Toxicity and irritation tests were studied at Cell and animal toxicity laboratory, Faculty of Pharmacy, University of Tehran Medical Sciences, Tehran P.
The standards for irritation and toxicity experiments and methods were ES, BN ISO 10; and BS EN ISO All experimental protocols were approved by IR-FDA and Research Ethics Committees of Tabriz University of Medical Sciences with Approval ID: IR. All methods were carried out by relevant guidelines and regulations.
Name of the chemical and methods to anesthetize the animal is reported in detail in the materials and method section. All documents related to irritation and toxicity tests and ethics approval are included as supplementary files.
Also, the statements are included in the manuscript. We confirm that all experimental protocols were approved by IR-FDA and Dr. Ostad from the Cell and animal toxicity laboratory, Faculty of Pharmacy, University of Tehran Medical Sciences, Tehran. All methods were carried out in accordance with the following standards: Antibacterial Tests: EN, Antifungal Tests: EN, Antiviral Tests: EN , ISIRI , EN All mentioned standards have been included in the manuscript and test results are included as supplementary files.
Irritation and toxicity methods and materials are attached as supplementary files. Also, Figure Number 6 has been taken by Prof. Ostad at Tehran University of medical sciences, Iran. other pictures taken by Prof.
Ostad are attached as supplementary files. Amodiaquine is an orally active 4-aminoquinoline derivative with antimalarial and anti-inflammatory properties. The molecular Formula of Amodiaquine is C 20 H 22 ClN 3 O and its chemical structure is shown in Fig. However, the Zn atoms in the water environment are not stable and convert to ZnO particles.
The surface of nanoparticles is covered by PVP in the first step. In the second part, the polymer chains were instituted by an amodiaquine ligand. As Fig.
These groups are —OH, —Cl, and —NH. Figure 2. Shows TEM image of synthesized nanoparticles. As the figure shows there are two types of nanoparticles in the image. Ag nanoparticles are 35 nm and a shell can be observed around the particles. There are ZnO nanoparticles beside the Ag nanoparticles with a diameter of As the figure shows the synthesized materials have absorption peaks at , , and nm.
However, the bands are relatively broad and it covers all ranges of the UV-B and UV-Aspectra. This means using it on the skin can act as a sunscreen. The colloid dried at 80 °C for recording the XRD diffraction pattern Fig.
As the Figure shows, all the diffraction peaks correspond to ZnO JCPDS Card No. FT-IR spectra related to ZnO NPs, Ag NPs, Amodiaquine, and the synthesized NPs are shown in Fig. FT-IR spectrum of the synthesized NPs shows existing of Ag, ZnO, and Amodiaquine absorption bands.
test irritation A the first day after removing the Fur without exposure with colloid B 1 weak after exposure with the synthesized colloid C 2 weeks after exposure D 4 weeks after exposure.
The application lasted for 4 h for a simple irritation test and 3 days for a repeated irritation test. The skin reactions were evaluated 1, 24, 48, and 72 h after the beginning of the treatment. No edema or erythema was observed in all animals treated with the test material.
The positive control group shows edema erythema as mentioned in Table 1. Based on the results, interpreted according to BS EN ISO ; , the test substance did not cause any irritant effects after 24, 48, and 72 h on the skin.
Figure 4 shows guinea pigs used for the irritation test of the synthesized nanoparticles. Table 2 shows the general cage-side observations for the parameters studied.
Bodyweight is an important factor to monitor the health of an animal. Loss in body weight is frequently the first indicator of the onset of an adverse effect.
It is considered the dose, which produces a minimum toxic effect, irrespective of whether or not it is accompanied by any other changes. All the animals from the treated groups did not show any significant decrease in body weights for all 14 days as compared with the 0- day values.
There was no significant change in food and water intake of the test animals at all dose levels for all days. From the results of this study, it is observed that there is no change in body weight, food and water consumption by the animals from all dose groups, and there was no mortality recorded even at the highest surface area level i.
So, the synthesized drug has been considered practically nontoxic from this route of administration. The toxicity of the synthesized material was tested based on the Draize eye protocol on the eyes of white rabbits and no biochemical, behavioral, or pathological changes were observed during 2 months.
The Draize rabbit eye test is an acute toxicity test for assessing the effects of chemicals, substances, and mixtures in terms of their potential to cause irritancy or damage to the body cells. Metals and metal ions tend to bind to O, N, and S-ligand atoms through interactions that are often strong and selective.
These interactions are based on coordination chemistry. Hard-soft acid-base theory HSAB theory is another concept that plays a fundamental role in the reactivity of metals.
The HSAB classification, which has been determined empirically, provides an arrangement of transition metals according to their preferences for specific organic ligands.
For example, soft acids such as Hg II , Cu I , Ag I , and Cd II and borderline acids such as Co II , Ni II , Cu II and Zn II tend to bond tightly with soft bases, such as sulfhydryl groups RSH found in proteins As a result, the antibacterial toxicity of these metals is roughly proportional to their affinity for S atoms.
The Covid virus has spike glycoprotein S , membrane M , envelope E , and nucleocapsid N proteins, in its structure. Surface proteins have sulfhydryl groups And Ag and Zn atoms can inhibit viral infection by blocking the spike protein and angiotensin of the SARS-CoV which can lead to the formation of protein disulfides and the depletion of antioxidant reserves, particularly glutathione, within microbial cells.
Also, in addition to the destruction of the active site, metal substitutions at non-catalytic metal-binding sites can inhibit enzyme activity.
Also, a few papers reported that Aqueous ZnO suspensions have also been reported to increase the levels of reactive oxygen species ROS , mainly hydroxyl radicals, which contribute to the antibacterial activity of ZnO nanoparticles In addition, these nanoparticles can enter the cellular cytoplasm and interact with the nucleic acids and disrupt the performance of the virus and possibly inhibit viral infection from infected cells to non-infected cells Further studies are needed to further investigate the antiviral performance of the synthesized nanoparticles on SARS - CoV for in-depth clarification.
Table 3 shows the effect of synthesized nanomaterials on examined bacteria. The results for the effect of the synthesized nanomaterial on E. coli bacteria in the concentrations of 8. The comparison of the obtained results with other reported nanoparticles indicates a much higher affectivity of the synthesized nanomaterials For example, the percentage of antimicrobial activity at 0.
The percentage of antimicrobial activity at 0. coli and B. Effect of synthesized nanoparticles on E. coli , Staphylococcus aureus , Enterococcus hira , and Pseudomonas aeruginosa , in different concentrations the concentrations of 8. Table 4 shows the effect of synthesized nanomaterials on examined fungi.
This is more than 8. Table 5 shows the effect of synthesized nanomaterials on examined viruses. This reduction is more than 7.
And this means the produced medicine can be applied for inhibiting of Covid 19 easily. The medicine was tested as a mouthwash on people, of whom had symptoms of Covid 19 and who did not have symptoms but were caring for the patient.
Of the people who had symptoms, 28 had more than 70 percent lung involvement. People with mild symptoms all recovered completely after 9 gargles three times a day. People with more symptoms recovered after 9 gargles with medication prescribed by a doctor.
And people who did not have symptoms did not get sick despite being exposed to the virus. Antibacterial, antiviral, antifungal, and toxicity effects of synthesized nano colloid in different concentrations were investigated.
As the results show, the synthesized nanomaterial with a concentration of µg per milliliter did not show any toxicity. This concentration of synthesized colloids also shows very good antifungal results.
The antiviral effects of the synthesized nano colloid were evaluated on H1N1, herpes simplex, and Covid viruses. In all of these cases, the synthesized nanomaterials in less than 30 s show a significant reduction of the virus, which in the case of Covid 19 is 7. The clinical results of the synthesized colloid as a mouthwash show promising effects in curing and preventing the progression of Covid 19 disease.
We provide information on the search routines used to locate, and then download, those records. Those instructions allow an interested party with a suitable license to those databases to regenerate comparable datasets. Galdiero, S. et al. Silver nanoparticles as potential antiviral agents, molecules.
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Yeh, Y. Nano-based drug delivery or targeting to eradicate bacteria for infection mitigation: A review of recent advances. Additionally, among all the flavonoids available in the traditional Chinese herb, Exocarpium Citri grandis, naringin 56 possessed the greatest potential for application in reducing the respiratory symptoms caused by COVID In this study some notable features of naringin 56 were revealed, namely that it could improve lung function, alleviate acute lung injury, have effects in attenuating pulmonary fibrosis, and enhance the antiviral immune response through its catabolite HPPA Su et al.
An in silico study proved that quercetin 6 , hispidulin 3 , and cirsimaritin 57 exhibited better potential inhibition than hydroxy-chloroquine potential inhibition against the COVID main protease active site and ACE2 Omar et al. Moreover, according to the results of another in silico study in which 8, small molecule candidates of known drugs and natural products were screened, quercetin 6 was among the top five most potent compounds for binding strongly to the S-protein ACE2 Smith and Smith, Based on the results of a computational study in which a library of phenolic natural compounds comprising 80 flavonoids was investigated against SARS-CoV-2 main protease, some other flavonoids including hesperidin 58 , rutin 8 , diosmin 59 and apiin 60 were found to have the potential to bind to the active site.
Hesperidin was reported to have the best binding affinity to the main protease Adem et al. Also, in another in silico study, rutin 8 showed notable inhibitory activity against SARS-CoV-2 main protease Das et al. Despite the notable effects of quercetin 6 and its derivatives, there are some issues which should be considered.
Quercetin and its glucosides found in plants were preferred for interaction with proteins Day et al. It has been proven that, despite administration of a high oral dose of quercetin, plasma contained traces of the glycoside due to biotransformation in the gastrointestinal tract Mullen et al.
However, by using a nasal spray containing quercetin glucosides in a suitable form, the appropriate concentration can be delivered to the active sites Zhao et al. Later in , administration of quercetin was recommended to be done directly through alternative routes such as a nasal or throat spray to be effective in clinical trials Williamson and Kerimi, As mentioned earlier, there is more than one host-cell receptor which has been reported to be recognized by the viral spike protein.
HSPA5, also termed GRP78 or BiP, is one of these receptors in the cell-surface. Some active components found in some natural products have been tested against HSPA5 in silico.
Based on the obtained results, some phytoestrogens diadiazin, genistein, formontein, and biochanin A and estrogens have the best binding affinities to HSPA5 Elfiky, According to the results of a computational study there are several natural molecules like δ-viniferin 66 , myricitrin 61 , taiwanhomoflavone A, lactucopicrin oxalate, nympholide A, afzelin, biorobin, hesperidin, and phyllaemblicin B that strongly bind to the SARS-CoV-2 M Pro.
The flavonoid myricitrin 61 showed strong binding with SARS-CoV-2 M Pro and also high solubility and bioavailability. Interestingly, this compound also showed strong binding with other potential targets of SARS-CoV-2 infection like viral receptor ACE-2 and RNA dependent RNA polymerase RdRp Joshi et al.
An in silico study with a focus on three target proteins important in the life cycle of SARS-CoV-2, namely Spike glycoprotein, main protease and RNA-dependent RNA-polymerase was performed. The results showed that silybin 62 , an active constituent found in Silybum marianum , showed binding affinity with targets in SARS-CoV Also, withaferin A from Withania somnifera showed significant binding to the target proteins Pandit and Latha, According to many studies, PLpro and 3CLpro can be considered as important targets for antiviral drugs against coronaviruses.
About 38 drugs and analogues with antiviral activity and 55 of natural origin were screened for inhibitory activities against PLpro and 3CLpro. The results showed that saikosaponin D 36 possessed the highest affinity to 3 CL-PRO; Conversely, amentoflavone 63 seemed to be a promising inhibitor of PLpro Contreras-Puentes and Alvíz-Amador, Agsirga is a traditional Mongolian medicine commonly used to treat tumor and cancer Cheng et al.
Curcumin 65 , the principal curcuminoid in the rhizome of Curcuma longa L. This compound has been proven to bind to the active site of SARS-CoV-2 main protease Das et al. Also, δ-viniferin 66 showed strong binding with the SARS-CoV-2 main protease and strong binding affinity to ACE-2 and RNA dependent RNA polymerase RdRp Joshi et al.
As mentioned before¸ TMPRSS2 is essential for viral spread and pathogenicity and a TMPRSS2 inhibitor might constitute a treatment option. A virtual screening of natural products against TMPRSS2 indicated that among compounds with promising features, geniposide 67 can be considered as the best drug candidate for drug development.
Geniposide 67 is an iridoid found in the Gardenia genus Rubiaceae and is endemic in Central America and China Rahman et al. Eight compounds found in rhizomes of Alpinia officinarum and ginger were identified as potential inhibitors of SARS-CoV-2 PLpro.
Binding affinities to closed and open conformer of PLpro were evaluated. Based on the obtained results, five compounds from the rhizome of Alpinia officinarum were identified.
Compound 68 binds with the highest affinity to the open conformer of SARS-Cov-2 PLpro and three compounds including 8-gingerol, gingerol and 6-gingerol from ginger were identified to be potent inhibitors of PLpro Goswami et al.
Resveratrol 69 is a stilbenoid commonly found in Vitis species grapes , red wine and some other plants Akinwumi et al. There have been some studies assessing the impact of resveratrol on SARS-CoV-2 ACE2 activity.
An in silico study revealed that resveratrol showed significant binding with ACE2 over other tested stilbenoids in the study Wahedi et al.
Also, resveratrol 69 and pterostilbene 70 inhibited SARS-CoV-2 infection in a Vero-E6 model. The compounds interfered with the viral infectious cycle and significantly inhibited COVID infection in primary human bronchial epithelial cells cultured under air liquid interface conditions ter Ellen et al.
The structures of natural products against SARS-CoV-2 are demonstrated in Figure 3. The efficacy of some natural compounds and medicinal plants has been tested clinically. Based on biological therapeutic activities, resveratrol 69 has been suggested as a potential treatment adjunct for COVID Filardo et al.
Resveratrol 69 can reduce copper II to copper I thereby generating highly unstable free-radicals which can degrade cell-free chromatin and can lead to prevention of endotoxin sepsis in mice.
In one study, a nearly two-fold reduction in mortality following treatment with resveratrol-copper was observed. In this study thirty patients with severe COVID received, in addition to standard care, resveratrol 69 and copper at doses of 5.
Lianhua Qingwen prescription capsules or granules is an innovative patented Chinese medicine that is composed of 11 herbs with gypsum and menthol, and this preparation had antiviral activities against viral respiratory infections. It includes Forsythia suspensa Thunb.
Vahl Lianqiao , Lonicera japonica Thunb Jinyinhua , Ephedra sinica Stapf Mahuang , Armeniacae Amarum Semen Kuxingren , Gypsum Fibrosuum Shigao , Isatis tinctoria L Banlangen , Dryopteridis Crassirhizomatis Rhizoma Mianmaguanzhong , Houttuynia cordata Thunb Yuxingcao , Pogostemon cablin Blanco Benth Guanghuoxiang , Rheum palmatum L Dahuang , Rhodiola rosea Linn Hongjingtian , Mentha haplocalyx Briq Bohe , Glycyrrhiza uralensis Fisch Gancao with a herbal ratio of g: g: 57 g: 57 g: g: g: g: g: 57 g: 34 g: 57 g: 5 g: 57 g, which is recorded in the Chinese Pharmacopeia.
A study of patients who received Lianhua Qinwen Capsules in combination with basic treatment showed the recovery rate in treatment group was significantly higher than the control group. Time of recovery of symptoms, fever, fatigue, and coughing was remarkably shorter in treatment Hu et al.
Also, another study reported that Lianhua Qingwen Granules could inhibit fever and cough, reduce their duration and improve individual symptoms Yao et al.
Also, some other traditional Chinese medicines were found to improve patient recovery Luo et al. SARS is a respiratory illness caused by severe acute respiratory syndrome coronavirus SARS-CoV Drosten et al.
There is evidence that supports medicinal plants and natural products in having beneficial effects in the treatment or prevention of SARS. In , a study revealed that taking a modified formula of two Chinese herbal medicines Yupingfeng Powder and Sangju Decoction resulted in the prevention of SARS-CoV Lau et al.
None of the health care workers using the supplement contracted SARS, in comparison to 0. Improvements in influenza-like symptoms in addition to quality of life measurements were also noted among herbal supplement users Lau et al.
As mentioned before, PLpro can be considered as an important target for antiviral agents Lenschow et al. Paulownia tomentosa Thunb. Flavonoids possess hydrophobic aromatic rings and hydrophilic hydroxyl groups, so they have a wide range of binding affinity to SARS-CoV 3CLpro.
The binding affinity and mode of the chromenone moiety depends on the presence of carbohydrate groups Jo et al. Many small molecules capable of targeting PLpro have been isolated from the methanol extracts of the fruits of the Paulownia tree P. Five new geranylated flavonoids, including tomentin A-E 71—75 were among these compounds.
They all contain a 3,4-dihydro-2H-pyran group. Most isolated compounds 71 — 82 were evaluated as PLpro inhibitors with IC 50 values ranging between 5. All new compounds with a dihydro-2H-pyran group in their structure showed better inhibition than their parent compounds Cho et al.
According to the results of an induced-fit docking experiment, the presence of an additional 8-hydroxyl group of herbacetin 83 was anticipated to be critical for its high binding affinity around the S1 and S2 sites.
The occupation of the S1 and S2 sites by carbohydrate groups of rhoifolin 84 and pectolinarin 85 was expected to be an additional way to achieve a high affinity to SARS-CoV 3CLpro in glycosylated flavonoids Jo et al.
In , a natural product library comprising compounds was screened for inhibitory activity against 3CLPro. Also the 3CLPro-inhibitory activity of extracts from different types of teas, including green tea, oolong tea, Puer tea and black tea was further investigated.
Two types of tea, including Puer and black tea, showed inhibitory activities against 3CLPro. Moreover, some biflavonoids from Torreya nucifera L. are reported to be active against the 3CLpro. The biflavone amentoflavone 87 was the most potent inhibitor of the 3CLpro Ryu et al.
Also, quercetin 6 , epigallocatechin gallate 10 , and gallocatechin gallate GCG 88 isolated from the yeast Pichia pastoris displayed good inhibition of 3CLpro Nguyen et al. Additionally, the structure—activity relationship of eight new derivatives of quercetin 6 was investigated with the help of molecular modeling.
Results revealed that the bioactivity of the derivatives was reduced by the removal of the 7-hydroxy group of the quercetin 6 moiety and acetoxylation of the sugar moiety Chen et al. Xanthoangelol E 88 , isolated from Angelica keiskei Miq. Compound 90 showed 3CLpro and PLpro inhibitory activity with IC 50 values of Further protein-inhibitor mechanistic analysis revealed that inhibition properties of chalcones to the SARS-CoV 3CLpro seem to be competitive, whereas non-competitive inhibition was observed with the SARS-CoV PLpro Park et al.
Papyriflavonol A 91 is a polyphenol isolated from Broussonetia papyrifera L. ex Vent. It acted as an inhibitor of PLpro with an IC 50 value of 3. These phytochemicals were identified as replication inhibitors of SARS-CoV by inhibiting PLpro in a dose-dependent manner with IC 50 ranging between 4.
Myricetin 97 and scutellarein 98 are two naturally-occurring flavonoids. Both compounds act as potent inhibitors of the SARS-CoV helicase protein in vitro by affecting the ATPase activity Yu et al. Some natural products showed moderate inhibitory activity against SARS-CoV, for instance procyanidin B1 99 , procyanidin A2 , and cinnamtannin B1 extracted from Cinnamon cortex dried bark of Cinnamomum verum J.
Presl and the ethanol extract of Cinnamon cortex have been reported with a low or moderate anti-SARS-CoV activity Zhuang et al. The abietane type diterpenoids isolated from the ethanol extract of Salvia miltiorrhiza Bunge such as tanshinone IIA , tanshinone IIB , methyl tanshinonate , cryptotanshinone , tanshinone I , dihydrotanshinone I , and rosmariquinone were identified as inhibitors of the SARS-CoV 3CLpro and PLpro.
The inhibitory activity of all seven compounds — was considerable ranging from 0. Interestingly, the inhibition was selective because no inhibitory effects against other proteases were observed Park et al.
According to the results of an investigation on phytocompounds in , 20 compounds including ten diterpenoids, two sesquiterpenoids, two triterpenoids, five lignoids and one curcumin were identified to be active against SARS-CoV in a cell-based assay of cytopathogenic effect on Vero E6 cells.
All compounds exhibited significant inhibition on SARS-CoV 3CLpro Wen et al. Glycyrrhizin 47 is the principal triterpenoid isolated from licorice Glycyrrhiza glabra L. In , the results of an investigation showed that glycyrrhizin 47 acted as a potent inhibitor of SARS-CoV replication in Vero cells with a selectivity index of Although glycyrrhizin 47 had a low selectivity index, it was a significantly potent inhibitor of replication of all the viruses tested and few toxic effects of glycyrrhizin 47 were reported Cinatl et al.
In , some commercial antiviral agents and purified compounds extracted from traditional Chinese medicinal herbs were screened against SARS-CoV. Glycyrrhizin 47 and some other compounds including interferon-beta-1a, leukocytic interferon-alpha, ribavirin, rimantadine, lopinavir and baicalin showed antiviral activity against SARS-CoV.
The two interferons were only effective when the cells were pre-incubated with the drugs 16 h before viral inoculation, and antiviral activity depended on the cell lines used.
Vero, Vero E6, and fRhK-4 cell lines were used in this investigation. Inhibitory activities were not observed for artesunate, glycyrrhizin 47 and chlorogenic acid in fRhK-4 cell line. Ribavirin, baicalin and lopinavir were less active in the Vero-E6 cell line while glycyrrhizin, rimandatine, leukocytic interferon-alpha and interferon-beta were more active.
Since antiviral activity could be shown for most of the agents in Vero cells, Vero cells were used instead of Vero E6 or fRhK-4 cells for the plaque reduction assay Chen et al.
Some alkaloids have been reported to be active against SARS-CoV. Six cinnamic amides — were isolated from Tribulus terrestris L.
These compounds were proven to be active against SARS-CoV PLpro with IC 50 values in the range Indigo is an alkaloid isolated from Isatis indigotica with the ability to block the cleavage processing of the 3CLpro Lin et al. In , antiviral activities of more than Chinese medicinal herb extracts against SARS-CoV were evaluated.
had the most potent antiviral activity against SARS-CoV. The process of further purification in order to identify the active compound led to the isolation and identification of an alkaloid, lycorine , as a potent antiviral compound against SARS-CoV with EC50 ranging from 2.
In the cytotoxicity assay, this compound had a CC50 value of 14, Aloeemodin and hesperetin 55 are two phenolic compounds, isolated from Isatis indigotica Fortune ex Lindl.
root extract, that inhibit cleavage activity of the 3CLpro in dose-dependent manners. Sinigrin , and beta-sitosterol are other isolated compounds with the ability to block the cleavage processing of the 3CLpro in cell-free and cell-based assays Lin et al.
The inhibitory action of dieckol , a phlorotannin isolated from the algal species Ecklonia cava , against SARS-CoV 3CLpro was investigated. Additionally, in silico molecular docking simulation of dieckol was performed to evaluate its interactions with protein residues in the original ligand-binding site.
The findings from docking experiments confirmed the important inhibitory effect of this compound against SARS-CoV 3CLpro Park et al. Psoralidin is a natural phenolic compound isolated from Psoralea corylifolia L. which has been proved to inhibit PLproof SARS-CoV Kim et al.
Emodin is an anthraquinone which significantly blocked the S protein, and also ACE2 interaction, in a dose-dependent manner.
It was derived from the genera Rheum officinale Baill. and Polygonum multiflorum Thunb current scientific name Reynoutria multiflora Thunb. Emodin inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells Ho et al.
Wu and co-workers highlighted potential inhibitors against SARS-CoV and identified numerous potent SARS-CoV inhibitors through screening of a library of natural products. These compounds showed inhibitory activity against viral replication.
Some active compounds were able to inhibit the 3CL protease and viral entry Wu et al. Moreover, the potential activity of the extracts of some plants against SARS-CoV has been studied. Houttuynia cordata Thunb.
water extract exhibited significant inhibitory effects on SARS-CoV 3CLpro Lau et al. There is evidence of H. cordata protecting cells against other coronaviruses as well Yin et al. Methanol extracts of Cimicifuga rhizoma, Phellodendron cortex, and Sophora subprostrata radix have been identified as inhibitors of RNA synthesis and N and S expression in vitro Kim et al.
The structures of mentioned natural compounds against SARS-CoV are shown in Figure 4. MERS-CoV, belonging to β-CoVs, is mainly endemic in the Middle East but it can also spread outside this region.
In , compounds derived from natural products, either animal or plant, were screened for their ability to block MERS-CoV entry. Of all tested compounds, dihydrotanshinone exhibited antiviral activity against MERS-CoV in the post-attachment assay.
Also, it showed antiviral activities in the pre-attachment assay. Therefore dihydrotanshinone may have dual inhibitory effects that block virus entry and inhibit S proteins Kim et al. The binding affinity of four compounds isolated from Coriandrum sativum L.
with six proteins of MERS-CoV was evaluated via in silico methods. Virtual screening and molecular docking results showed that dodecanal had the highest binding affinity with all the selected proteins Rao et al. In , a high-throughput screening of potential inhibitors of CoVs in vitro resulted in the identification of seven compounds as inhibitors of the replication of CoVs.
Among the seven inhibitors, the alkaloid emetine exhibited the strongest anti-MERS-CoV activity with an EC50 value of 0. It acted as an entry inhibitor blocking MERS-CoV-S-mediated infection Shen et al. Natural products against coronaviruses are summarized in Table 2 and their structures are shown in Figure 5.
At the present time no specific anti-COVID drugs are available and research communities, countries, and public health organizations are investigating all means to combat this globally transmitted pandemic.
Early implementation of strict physical distancing and sanitation protocols has played a role in reducing the incidence of COVID in many parts of the world Islam et al. Evaluation of current promising antiviral agents is a necessary strategy to discover efficient treatments against this disease.
Natural compounds are widely recognized as complex structures, crafted by evolutionary processes to interact with macromolecular targets. Over the past years, investigations all over the world have generated renewed interest in the search for novel antiviral agents from plant origin.
With consideration of the provided information on influenza viruses, SARS-CoV, and Mers-CoV, the new SARS-CoV-2 virus, which shows a broad clinical spectrum and dramatic expansion, might be controlled based on genomic organization similarities.
In this survey we summarized recently reported discoveries of natural compounds with activity against respiratory viruses. We introduced natural compounds as possible therapies to fight against respiratory viruses, including influenza virus, SARS-CoV, MERS-CoV and SARS-CoV Different groups of natural products have antiviral activities but the majority of these compounds belong to the alkaloid, flavonoid and terpenoid families.
Although most of the natural compounds listed in this assay are potential inhibitors of COVID, the results are mostly based on theoretical or in vitro research. Most current research does not present analytical validation.
Some natural products, including xanthoangelol E 88 , hispidulin 3 , quercetin 6 , rutin 8 , saikosaponin D 36 , glycyrrhizin 47 , methyl rosmarinate 27 and hesperetin 55 showed antiviral activities against different respiratory viruses in vitro and in vivo.
These compounds can be recommended as potential lead candidates to prioritise for investigation. Additionally, resveratrol 69 is a natural compound which showed promising activity against COVID in the clinical setting. In some cases the maximal suppression of virus infection and replication can be obtained by using a combination of drugs with different mechanisms of action.
Natural products and herbal medicine can be considered as important drugs which can be used in combination with basic antiviral treatment. Despite several existing reports about natural products and their antiviral activities, working with phytochemicals requires expertize and there are many challenges in working with natural compounds.
For instance, the isolation, purification, and identification of the structures of these compounds might be paved with challenges. Also, the bioavailability of natural products should be considered before embarking on expensive clinical trials.
Other issues include difficulties in prediction of a suitable dosage for these compounds, modes of drug delivery, and the outcome of the combination of two or more of these natural products.
The flavonoid quercetin 6 is a highly promising compound on the basis of its antiviral activity against influenza A, SARS-CoV, and COVID Future studies should focus on appropriate methods of delivery to combat respiratory viruses, such as nasal or throat sprays, and in vivo efficacy.
The structure-based drug design approach is recommended to allow synthetic chemists to develop effective anti-COVID agents. In this regard, the relationship between structure and activity of the compound can be a viable strategy and guidance to create a broad range of anti-respiratory viral compounds.
Some previously mentioned studies have given different perspectives, such as activity-guided fractionation, which can be used as a tactic to discover anti-COVID medicines. Accordingly, screening programs may be a rational way to test traditionally used plants all over the world by working on a pseudovirus of COVID Medicinal plants are known as a key natural resource for therapeutic agents.
Whilst the future evolution of the current coronavirus pandemic remains unpredictable, beside the public health strategies there is an urgent need for global interdisciplinary cooperation between chemists, microbiologists, botanists and biochemists in order to find natural medicines against COVID and to combat the current challenges, even during inter-epidemic periods.
MAA and PM co-defined the research theme. MO, MK, and MM carried out in-depth study on the research papers, collaborated on the associated data collection and drafted the manuscript. MAA, PM, SNE, and LJM revised the manuscript critically for editorial and important intellectual content.
All authors have seen and approved the manuscript. 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.
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Grienke, U. Here are the ten antiviral foods that will give you the balanced diet necessary for optimal wellness. Luckily for us, these molecules make garlic one of the most delicious antiviral foods out there 2. Research shows that these compounds can impede the growth of influenza A and influenza B, as well as herpes and HIV.
In the case of HIV, ajoene, in particular, has proven particularly helpful. Early HIV studies suggest ajoene prevents the irregular cellular processes triggered by HIV-infected cells 3. There are many garlic supplements out there.
However, nothing beats raw garlic. Garlic is easy to incorporate into a healthy diet. It adds flavor to anything and builds a strong immune system.
So, stock up on this spice! This licorice-flavored spice is rich in shikimic acid. Shikimic acid has potent antiviral properties. This spice has a very powerful flavor. A little can go a long way with this Chinese herb. They consume an abundance of natural products, whole foods, and healthy fatty acids.
One of their greatest sources of these desirable health habits is the olive. Olive leaves are one of the most abundant sources of oleuropein.
Studies involving this molecule found that it shows significant effects against respiratory syntactical virus and para-influenza type 3 virus 5. While olive oil has less oleuropein than olive leaf, it has a considerable amount of healthy fatty acids that repair our gut and keep our immune system strong.
Up the antioxidant effects and give free radicals a scare with a delicious garlic oil infusion! Ginger is a staple in Traditional Chinese Medicine. This tangy root can bring life to any stir-fry or give your water a fizzy flavor.
It also has excellent antiviral capabilities that makes this root essential for a healthy daily diet. One study found that ginger helped improve the cells in both the upper respiratory tract HEp-2 cells and lower respiratory tract A cells 6.
Furthermore, analysts noted that ginger caused cells to secrete Interferon-beta IFN-β. IFN-β is a polypeptide that has antiviral capabilities because it regulates DNA encryption 7. So, it can help block a viral attack. An unsung hero in antiviral foods is oregano oil.
Oregano plants are one of the most flavorful and effective antiviral herbs in the world. Extracts from this Italian herb are rich in antioxidants and other healing compounds that fight off free radicals.
Namely, carvacrol can stop nonenveloped murine norovirus MNV in its tracks 8. MNV is a precursor to noroviruses. Researchers noted that antiviral effects can happen within an hour of ingesting oregano oil.
Oregano oil is highly abrasive on the skin. Make sure to mix it with a thicker carrier oil if you are using it as a chest rub. Excellent choices for carrier oils include coconut oil and olive oil.
Be sure to add in some lemon balm for the scent of citrus fruits and an extra dose of antiviral properties! The sea-based superfood spirulina is one of the most versatile antiviral foods. You can add spirulina powder to a variety of superfood smoothies.
If you never thought about doing so, it might be time to reconsider. One study looked at the effects of spirulina on three predominant types of influenza 9. Considerable evidence suggests that after one hour, the blue algae inhibited virus replication.
Many of the antiviral benefits of spirulina are attributed to its high levels of cyanovirin-N. This protein has shown promise in slowing down the progression of HIV to AIDS This plant-based food is also a great source of Vitamin E.
Vitamin E not only helps fight off free radicals but it helps convert our food to energy.
In terms of ending Strpng Strong anti-viral the pandemic, most attention has gone to very effective Antioxidant and respiratory health tSrong vaccines, Antioxidant and respiratory health, and social distancing. Read anti-virsl to Caffeine and memory enhancement more about natural anti-viarl options, from antiviral herbs to ozone therapy and beyond. Would you rather listen than read? Get an audio version of this guide on The WellBe Podcast. As the names suggest, bacterial infections are caused by bad bacteria as opposed to good bacteria, like probioticswhile viral infections are caused by viruses. Bacteria are tiny, single-celled microorganisms that live basically everywhere, including in your body hello, gut microbiome!
The emergence of Strong anti-viral pneumonia caused by a Strong anti-viral coronavirus CoV Strogn, known Strnog the novel coronavirus nCoVVegan meal delivery services Strong anti-viral a contagious acute respiratory infectious disease in December in Wuhan, Hubei Province, China. Its alarmingly quick Strlng to many countries across the world anti-virql a considerable percentage Heart health equipment morbidity and mortality made the World Health Organization recognize it as a pandemic on March 11, The perceived risk of infection has led many research groups to study COVID from different aspects. In this literature review, the phylogenetics and taxonomy of COVID coronavirus, epidemiology, and respiratory viruses similar to COVID and their mode of action are documented in an approach to understand the behavior of the current virus. Moreover, we suggest targeting the receptors of SARS-CoV and SARS-CoV-2 such as ACE2 and other proteins including 3CLpro and PLpro for improving antiviral activity and immune response against COVID disease.
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