Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

Eupatin, a Flavonoid, Inhibits Coronavirus 3CL Protease and Replication.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than six million deaths worldwide since 2019. Although vaccines are available, novel variants of coronavirus are expected to appear continuously, and there is a need for a more effective remedy for coronavirus disease. In this report, we isolated eupatin from Inula japonica flowers and showed that it inhibits the coronavirus 3 chymotrypsin-like (3CL) protease as well as viral replication. We showed that eupatin treatment inhibits SARS-CoV-2 3CL-protease, and computational modeling demonstrated that it interacts with key residues of 3CL-protease. Further, the treatment decreased the number of plaques formed by human coronavirus OC43 (HCoV-OC43) infection and decreased viral protein and RNA levels in the media. These results indicate that eupatin inhibits coronavirus replication.

Aurones: A Promising Scaffold to Inhibit SARS-CoV-2 Replication.

Aurones are a small subgroup of flavonoids in which the basic C6-C3-C6 skeleton is arranged as (Z)-2-benzylidenebenzofuran-3(2H)-one. These compounds are structural isomers of flavones and flavonols, natural products reported as potent inhibitors of SARS-CoV-2 replication. Herein, we report the design, synthesis, and anti-SARS-CoV-2 activity of a series of 25 aurones bearing different oxygenated groups (OH, OCH3, OCH2OCH3, OCH2O, OCF2H, and OCH2C6H4R) at the A- and/or B-rings using cell-based screening assays. We observed that 12 of the 25 compounds exhibit EC50 < 3 µM (8e, 8h, 8j, 8k, 8l, 8m, 8p, 8q, 8r, 8w, 8x, and 8y), of which five presented EC50 < 1 µM (8h, 8m, 8p, 8q, and 8w) without evident cytotoxic effect in Calu-3 cells. The substitution of the A- and/or B-ring with OCH3, OCH2OCH3, and OCF2H groups seems beneficial for the antiviral activity, while the corresponding phenolic derivatives showed a significant decrease in the anti-SARS-CoV-2 activity. The most potent compound of the series, aurone 8q (EC50 = 0.4 µM, SI = 2441.3), is 2 to 3 times more effective than the polyphenolic flavonoids myricetin (2) and baicalein (1), respectively. Investigation of the five more active compounds as inhibitors of SARS-CoV-2 3CLpro based on molecular dynamic calculations suggested that these aurones should detach from the active site of 3CLpro, and, probably, they could bind to another SARS-CoV-2 protein target (either receptor or enzyme).

In silico screening of chalcones and flavonoids as potential inhibitors against yellow head virus 3C-like protease.

Yellow head virus (YHV) is one of the most important pathogens in prawn cultivation. The outbreak of YHV could potentially result in collapses in aquaculture industries. Although a flurry of development has been made in searching for preventive and therapeutic approaches against YHV, there is still no effective therapy available in the market. Previously, computational screening has suggested a few cancer drugs to be used as YHV protease (3CLpro) inhibitors. However, their toxic nature is still of concern. Here, we exploited various computational approaches, such as deep learning-based structural modeling, molecular docking, pharmacological prediction, and molecular dynamics simulation, to search for potential YHV 3CLpro inhibitors. A total of 272 chalcones and flavonoids were in silico screened using molecular docking. The bioavailability, toxicity, and specifically drug-likeness of hits were predicted. Among the hits, molecular dynamics simulation and trajectory analysis were performed to scrutinize the compounds with high binding affinity. Herein, the four selected compounds including chalcones cpd26, cpd31 and cpd50, and a flavonoid DN071_f could be novel potent compounds to prevent YHV and GAV propagation in shrimp. The molecular mechanism at the atomistic level is also enclosed that can be used to further antiviral development.

Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies.

OBJECTIVES: This scoping review aims to present flavonoid compounds' promising effects and possible mechanisms of action on potential therapeutic targets in the SARS-CoV-2 infection process. METHODS: A search of electronic databases such as PubMed and Scopus was carried out to evaluate the performance of substances from the flavonoid class at different stages of SARS-CoV-2 infection. RESULTS: The search strategy yielded 382 articles after the exclusion of duplicates. During the screening process, 265 records were deemed as irrelevant. At the end of the full-text appraisal, 37 studies were considered eligible for data extraction and qualitative synthesis. All the studies used virtual molecular docking models to verify the affinity of compounds from the flavonoid class with crucial proteins in the replication cycle of the SARS-CoV-2 virus (Spike protein, PLpro, 3CLpro/ MPro, RdRP, and inhibition of the host's ACE II receptor). The flavonoids with more targets and lowest binding energies were: orientin, quercetin, epigallocatechin, narcissoside, silymarin, neohesperidin, delphinidin-3,5-diglucoside, and delphinidin-3-sambubioside-5-glucoside. CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.

Computer Analysis of the Inhibition of ACE2 by Flavonoids and Identification of Their Potential Antiviral Pharmacophore Site.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time.

The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2.

New antiviral treatments are needed to deal with the unpredictable emergence of viruses. Furthermore, vaccines and antivirals are only available for just a few viral infections, and antiviral drug resistance is an increasing concern. Cyanidin (a natural product also called A18), a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, through its anti-inflammatory effects. Regarding its mechanism of action, A18 was identified as an IL-17A inhibitor, resulting in the attenuation of IL-17A signaling and associated diseases in mice. Importantly, A18 also inhibits the NF-κB signaling pathway in different cell types and conditions in vitro and in vivo. In this study, we report that A18 restricts RSV, HSV-1, canine coronavirus, and SARS-CoV-2 multiplication, indicating a broad-spectrum antiviral activity. We also found that A18 can control cytokine and NF-κB induction in RSV-infected cells independently of its antiviral activity. Furthermore, in mice infected with RSV, A18 not only significantly reduces viral titers in the lungs, but also diminishes lung injury. Thus, these results provide evidence that A18 could be used as a broad-spectrum antiviral and may contribute to the development of novel therapeutic targets to control these viral infections and pathogenesis.

A Comprehensive Review of Natural Flavonoids with Anti-SARS-CoV-2 Activity.

The COVID-19 pandemic caused by SARS-CoV-2 has majorly impacted public health and economies worldwide. Although several effective vaccines and drugs are now used to prevent and treat COVID-19, natural products, especially flavonoids, showed great therapeutic potential early in the pandemic and thus attracted particular attention. Quercetin, baicalein, baicalin, EGCG (epigallocatechin gallate), and luteolin are among the most studied flavonoids in this field. Flavonoids can directly or indirectly exert antiviral activities, such as the inhibition of virus invasion and the replication and inhibition of viral proteases. In addition, flavonoids can modulate the levels of interferon and proinflammatory factors. We have reviewed the previously reported relevant literature researching the pharmacological anti-SARS-CoV-2 activity of flavonoids where structures, classifications, synthetic pathways, and pharmacological effects are summarized. There is no doubt that flavonoids have great potential in the treatment of COVID-19. However, most of the current research is still in the theoretical stage. More studies are recommended to evaluate the efficacy and safety of flavonoids against SARS-CoV-2.

Immunopharmacological Activities of Luteolin in Chronic Diseases.

Flavonoids have been shown to have anti-oxidative effects, as well as other health benefits (e.g., anti-inflammatory and anti-tumor functions). Luteolin (3', 4', 5,7-tetrahydroxyflavone) is a flavonoid found in vegetables, fruits, flowers, and herbs, including celery, broccoli, green pepper, navel oranges, dandelion, peppermint, and rosemary. Luteolin has multiple useful effects, especially in regulating inflammation-related symptoms and diseases. In this paper, we summarize the studies about the immunopharmacological activity of luteolin on anti-inflammatory, anti-cardiovascular, anti-cancerous, and anti-neurodegenerative diseases published since 2018 and available in PubMed or Google Scholar. In this review, we also introduce some additional formulations of luteolin to improve its solubility and bioavailability.

Bioactive Azadirachta indica and Melia azedarach leaves extracts with anti-SARS-CoV-2 and antibacterial activities.

The leaves of Azadirachta indica L. and Melia azedarach L., belonging to Meliaceae family, have been shown to have medicinal benefits and are extensively employed in traditional folk medicine. Herein, HPLC analysis of the ethyl acetate fraction of the total methanolic extract emphasized the enrichment of both A. indica L., and M. azedarach L. leaves extracts with phenolic and flavonoids composites, respectively. Besides, 4 limonoids and 2 flavonoids were isolated using column chromatography. By assessing the in vitro antiviral activities of both total leaves extracts against Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2), it was found that A. indica L. and M. azedarach L. have robust anti-SARS-CoV-2 activities at low half-maximal inhibitory concentrations (IC50) of 8.451 and 6.922 µg/mL, respectively. Due to the high safety of A. indica L. and M. azedarach L. extracts with half-maximal cytotoxic concentrations (CC50) of 446.2 and 351.4 µg/ml, respectively, both displayed extraordinary selectivity indices (SI>50). A. indica L. and M. azedarach L. leaves extracts could induce antibacterial activities against both Gram-negative and positive bacterial strains. The minimal inhibitory concentrations of A. indica L. and M. azedarach L. leaves extracts varied from 25 to 100 mg/mL within 30 min contact time towards the tested bacteria. Our findings confirm the broad-spectrum medicinal value of A. indica L. and M. azedarach L. leaves extracts. Finally, additional in vivo investigations are highly recommended to confirm the anti-COVID-19 and antimicrobial activities of both plant extracts.

Promising Role of the Scutellaria baicalensis Root Hydroxyflavone-Baicalein in the Prevention and Treatment of Human Diseases.

Plant roots, due to a high content of natural antioxidants for many years, have been used in herbal medicine. It has been documented that the extract of Baikal skullcap (Scutellaria baicalensis) has hepatoprotective, calming, antiallergic, and anti-inflammatory properties. Flavonoid compounds found in the extract, including baicalein, have strong antiradical activity, which improves overall health and increases feelings of well-being. Plant-derived bioactive compounds with antioxidant activity have for a long time been used as an alternative source of medicines to treat oxidative stress-related diseases. In this review, we summarized the latest reports on one of the most important aglycones with respect to the pharmacological activity and high content in Baikal skullcap, which is 5,6,7-trihydroxyflavone (baicalein).

Anti-Entry Activity of Natural Flavonoids against SARS-CoV-2 by Targeting Spike RBD.

COVID-19 is still a global public health concern, and the SARS-CoV-2 mutations require more effective antiviral agents. In this study, the antiviral entry activity of thirty-one flavonoids was systematically evaluated by a SARS-CoV-2 pseudovirus model. Twenty-four flavonoids exhibited antiviral entry activity with IC50 values ranging from 10.27 to 172.63 µM and SI values ranging from 2.33 to 48.69. The structure-activity relationship of these flavonoids as SARS-CoV-2 entry inhibitors was comprehensively summarized. A subsequent biolayer interferometry assay indicated that flavonoids bind to viral spike RBD to block viral interaction with ACE2 receptor, and a molecular docking study also revealed that flavonols could bind to Pocket 3, the non-mutant regions of SARS-CoV-2 variants, suggesting that flavonols might be also active against virus variants. These natural flavonoids showed very low cytotoxic effects on human normal cell lines. Our findings suggested that natural flavonoids might be potential antiviral entry agents against SARS-CoV-2 via inactivating the viral spike. It is hoped that our study will provide some encouraging evidence for the use of natural flavonoids as disinfectants to prevent viral infections.

Multifaceted antiviral therapeutic potential of dietary flavonoids: Emerging trends and future perspectives.

Phytochemicals are the natural biomolecules produced by plants via primary or secondary metabolism, which have been known to have many potential health benefits to human beings. Flavonoids or phytoestrogens constitute a major group of such phytochemicals widely available in variety of vegetables, fruits, herbs, tea, and so forth, implicated in a variety of bio-pharmacological and biochemical activities against diseases including bacterial, viral, cancer, inflammatory, and autoimmune disorders. More recently, these natural biomolecules have been shown to have effective antiviral properties via therapeutically active ingredients within them, acting at different stages of infection. Current review emphasizes upon the role of these flavonoids in physiological functions, prevention and treatment of viral diseases. More so the review focuses specifically upon the antiviral effects exhibited by these natural biomolecules against RNA viruses including coronaviruses. Furthermore, the article would certainly provide a lead to the scientific community for the effective therapeutic antiviral use of flavonoids using potential cost-effective tools for improvement of the pharmacokinetics, bioavailability, and biodistribution of such compounds for the concrete action along with the promotion of human health.

In silico evaluation of flavonoids as potential inhibitors of SARS-CoV-2 main nonstructural proteins (Nsps)-amentoflavone as a multitarget candidate.

Despite the development of vaccines against COVID-19 disease and the multiple efforts to find efficient drugs as treatment for this virus, there are too many social, political, economic, and health inconveniences to incorporate a fully accessible plan of prevention and therapy against SARS-CoV-2. In this sense, it is necessary to find nutraceutical/pharmaceutical drugs as possible COVID-19 preventives/treatments. Based on their beneficial effects, flavonoids are one of the most promising compounds. Therefore, using virtual screening, 478 flavonoids obtained from the KEGG database were evaluated against non-structural proteins Nsp1, Nsp3, Nsp5, Nsp12, and Nsp15, which are essential for the virus-host cell infection, searching for possible multitarget flavonoids. Amentoflavone, a biflavonoid found mainly in Ginkgo biloba, Lobelia chinensis, and Byrsonima intermedia, can interact and bind with the five proteins, suggesting its potential as a multitarget inhibitor. Molecular docking calculations and structural analysis (RMSD, number of H bonds, and clustering) performed from molecular dynamics simulations of the amentoflavone-protein complex support this potential. The results shown here are theoretical evidence of the probable multitarget inhibition of non-structural proteins of SARS-CoV-2 by amentoflavone, which has wide availability, low cost, no side effects, and long history of use. These results are solid evidence for future in vitro and in vivo experiments aiming to validate amentoflavone as an inhibitor of the Nsp1, 3, 5, 12, and 15 of SARS-CoV-2.

Insights into the Pharmacological Effects of Flavonoids: The Systematic Review of Computer Modeling.

Computer modeling is a method that is widely used in scientific investigations to predict the biological activity, toxicity, pharmacokinetics, and synthesis strategy of compounds based on the structure of the molecule. This work is a systematic review of articles performed in accordance with the recommendations of PRISMA and contains information on computer modeling of the interaction of classical flavonoids with different biological targets. The review of used computational approaches is presented. Furthermore, the affinities of flavonoids to different targets that are associated with the infection, cardiovascular, and oncological diseases are discussed. Additionally, the methodology of bias risks in molecular docking research based on principles of evidentiary medicine was suggested and discussed. Based on this data, the most active groups of flavonoids and lead compounds for different targets were determined. It was concluded that flavonoids are a promising object for drug development and further research of pharmacology by in vitro, ex vivo, and in vivo models is required.

Flavonoids from the roots and rhizomes of Sophoratonkinensis and their in vitro anti-SARS-CoV-2 activity.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 µmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 µmol·L-1, respectively.

Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration.

Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-[Formula: see text]1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-[Formula: see text]1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-[Formula: see text]1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-[Formula: see text]1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration.

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline.

The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.

Pea eggplant (Solanum torvum Swartz) is a source of plant food polyphenols with SARS-CoV inhibiting potential.

Background: Pea eggplant (Solanum torvum Swartz) commonly known as turkey berry or 'terung pipit' in Malay is a vegetable plant widely consumed by the local community in Malaysia. The shrub bears pea-like turkey berry fruits (TBFs), rich in phytochemicals of medicinal interest. The TBF phytochemicals hold a wide spectrum of pharmacological properties. In this study, the TBF phytochemicals' potential inhibitory properties were evaluated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of the Coronavirus disease 2019 (COVID-19). The TBF polyphenols were screened against SARS-CoV receptors via molecular docking and the best receptor-ligand complex was validated further by molecular dynamics (MD) simulation. Method: The SARS-CoV receptor structure files (viral structural components) were retrieved from the Protein Data Bank (PDB) database: membrane protein (PDB ID: 3I6G), main protease (PDB ID: 5RE4), and spike glycoproteins (PDB ID: 6VXX and 6VYB). The receptor binding pocket regions were identified by Discovery Studio (BIOVIA) for targeted docking with TBF polyphenols (genistin, kaempferol, mellein, rhoifolin and scutellarein). The ligand and SARS-CoV family receptor structure files were pre-processed using the AutoDock tools. Molecular docking was performed with the Lamarckian genetic algorithm using AutoDock Vina 4.2 software. The best pose (ligand-receptor complex) from the molecular docking analysis was selected based on the minimum binding energy (MBE) and extent of structural interactions, as indicated by BIOVIA visualization tool. The selected complex was validated by a 100 ns MD simulation run using the GROMACS software. The dynamic behaviour and stability of the receptor-ligand complex were evaluated by the root mean square displacement (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), solvent accessible surface volume (SASV) and number of hydrogen bonds. Results: At RMSD = 0, the TBF polyphenols showed fairly strong physical interactions with SARS-CoV receptors under all possible combinations. The MBE of TBF polyphenol-bound SARS CoV complexes ranged from -4.6 to -8.3 kcal/mol. Analysis of the structural interactions showed the presence of hydrogen bonds, electrostatic and hydrophobic interactions between the receptor residues (RR) and ligands atoms. Based on the MBE values, the 3I6G-rhoifolin (MBE = -8.3 kcal/mol) and 5RE4-genistin (MBE = -7.6 kcal/mol) complexes were ranked with the least value. However, the latter showed a greater extent of interactions between the RRs and the ligand atoms and thus was further validated by MD simulation. The MD simulation parameters of the 5RE4-genistin complex over a 100 ns run indicated good structural stability with minimal flexibility within genistin binding pocket region. The findings suggest that S. torvum polyphenols hold good therapeutics potential in COVID-19 management.

In Silico Evaluation of Natural Flavonoids as a Potential Inhibitor of Coronavirus Disease.

The recent coronavirus disease (COVID-19) outbreak in Wuhan, China, has led to millions of infections and the death of approximately one million people. No targeted therapeutics are currently available, and only a few efficient treatment options are accessible. Many researchers are investigating active compounds from natural plant sources that may inhibit COVID-19 proliferation. Flavonoids are generally present in our diet, as well as traditional medicines and are effective against various diseases. Thus, here, we reviewed the potential of flavonoids against crucial proteins involved in the coronavirus infectious cycle. The fundamentals of coronaviruses, the structures of SARS-CoV-2, and the mechanism of its entry into the host's body have also been discussed. In silico studies have been successfully employed to study the interaction of flavonoids against COVID-19 Mpro, spike protein PLpro, and other interactive sites for its possible inhibition. Recent studies showed that many flavonoids such as hesperidin, amentoflavone, rutin, diosmin, apiin, and many other flavonoids have a higher affinity with Mpro and lower binding energy than currently used drugs such as hydroxylchloroquine, nelfinavir, ritonavir, and lopinavir. Thus, these compounds can be developed as specific therapeutic agents against COVID-19, but need further in vitro and in vivo studies to validate these compounds and pave the way for drug discovery.