The potential chemical structure of anti‐SARS‐CoV‐2 RNA‐dependent RNA polymerase

Lung, Jrhau; Yu, Lin; Yang, Yao‐Hsu; Chou, Yu Lun; Li, Shu; Cheng, Yu Ching; Liu, Hung Te; Wu, Ching Yuan

doi:10.1002/jmv.25761

Cited by 252 publications

(245 citation statements)

References 17 publications

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“…is -5.16 kcal/mol (15). In our previous study, we discovered that theaflavin (ZINC3978446) is a potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase (9). Moreover, we also found that theaflvin was able to dock in contact area in RBD of SARS-CoV-2.…”

Section: The Docking Binding Energy Between Dihydrotanshinone I and Smentioning

confidence: 91%

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The potential SARS-CoV-2 entry inhibitor

Lung

Lin

Chou

et al. 2020

Preprint

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Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. In coronaviruses, the receptor binding domain (RBD) in the distal part of S1 subunit of SARS-CoV-2 spike protein can directly bind to angiotensin converting enzyme 2 (ACE2). RBD promote viral entry into the host cells and is an important therapeutic target. In this study, we discovered that theaflavin showed the lower idock score (idock score: −7.95 kcal/mol). To confirm the result, we discovered that theaflavin showed FullFitness score of -991.21 kcal/mol and estimated ΔG of -8.53 kcal/mol for the most favorable interaction with contact area of SARS-CoV-2 RBD by SwissDock service. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were formed between theaflavin and Arg454, Phe456, Asn460, Cys480, Gln493, Asn501 and Val503 of SARS-CoV-2 RBD, near the direct contact area with ACE2. Our results suggest that theaflavin could be the candidate of SARS-CoV-2 entry inhibitor for further study. 4 Keywords： SARS-CoV-2, spike protein, receptor binding domain, theaflavin

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Section: The Docking Binding Energy Between Dihydrotanshinone I and Smentioning

confidence: 91%

“…In a recent study, we discovered that theaflavin possesses a potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase (9). Some Chinese medicinal compounds are also used for prophylaxis of SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

The potential SARS-CoV-2 entry inhibitor

Lung

Lin

Chou

et al. 2020

Preprint

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“…Few studies report on SARS-CoV-2, as expected given the short time since its emergence. However, a number of studies report on use of computer modelling for screening purposes (Liu and Zhou, 2005;Lung et al, 2020;Toney et al, 2004;Wang et al, 2007;Zhang et al, 2020). Typically, these models determine the free binding of energy between a ligand and a receptor (Forli et al, 2016), with a lower free binding energy indicating a stronger bond between the ligand and receptor.…”

Section: Inhibitors Of Sars-cov-2 (Covid-19)mentioning

confidence: 99%

Natural product-derived phytochemicals as potential agents against coronaviruses: A review

et al. 2020

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Coronaviruses are responsible for a growing economic, social and mortality burden, as the causative agent of diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), avian infectious bronchitis virus (IBV) and COVID-19. However, there is a lack of effective antiviral agents for many coronavirus strains. Naturally existing compounds provide a wealth of chemical diversity, including antiviral activity, and thus may have utility as therapeutic agents against coronaviral infections. The PubMed database was searched for papers including the keywords coronavirus, SARS or MERS, as well as traditional medicine, herbal, remedy or plants, with 55 primary research articles identified. The overwhelming majority of publications focussed on polar compounds. Compounds that show promise for the inhibition of coronavirus in humans include scutellarein, silvestrol, tryptanthrin, saikosaponin B 2 , quercetin, myricetin, caffeic acid, psoralidin, isobavachalcone, and lectins such as griffithsin. Other compounds such as lycorine may be suitable if a therapeutic level of antiviral activity can be achieved without exceeding toxic plasma concentrations. It was noted that the most promising small molecules identified as coronavirus inhibitors contained a conjugated fused ring structure with the majority being classified as being polyphenols.

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“…Theaflavin and its derivatives have also been shown to be equally effective as an antioxidant in comparison with catechins (40). Furthermore, it was shown to have lower docking scores against RNA dependent RNA polymerase of SARS-CoV-2 in a recent study (41). Though the most important finding was a strong hydrogen bond between its hydrogen (H8) and oxygen of His41 residue which also serves a critical role in forming the active catalytic site.…”

Section: Main Protease (Mpro Also Called 3cl Pro) (Pdb Code 6w6y)mentioning

confidence: 99%

Structure based drug discovery by virtual screening of 3699 compounds against the crystal structures of six key SARS-CoV-2 proteins

Saadat¹,

Mansoor

Naqvi

et al. 2020

Preprint

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BackgroundThe current Novel Coronavirus (SARS-CoV-2) pandemic is the third major outbreak of the 21st century which emerged in December 2019 from Wuhan, China. At present there are no known treatments or vaccines to cure or prevent the illness.ObjectiveThe objective of this study was to explore a list of potential drugs (herbal and antivirals) for their role in inhibiting activity and or replication of SARS-CoV-2 by using molecular docking onto the crystal structures of key viral proteins.MethodologyIn this study, we used molecular docking to estimate the binding affinities of 3699 drugs on the potential active sites of the 6 main SARS-CoV-2 proteins (Papain like protease, Main protease, ADP Ribose phosphatase, Spike protein, NSP-9 and NSP-10 to 16 complex). While other studies have mostly been performed on the homology models, we obtained the most recently submitted crystal structures of all 6 proteins from the protein data bank for this analysis.ResultsOur results showed the top ligands as Theasinensin A, Epigallocatechin, Theaflavin, Theasinensin A, Epigallocatechin and Favipiravir showing the highest binding affinities against papain-like protease, ADP ribose phosphatase, main protease, spike protein, RNA replicase (NSP-9) and methyl-transferase (NSP-16) respectively.ConclusionWe show that the compounds from our list with the greatest inhibitory potential against SARS-CoV-2 activity or replication include Theasinensin A, Epigallocatechin-3-gallate, Theaflavin, Favipiravir, Curucumin, Quercetin, Mitoxantrone, Amentoflavone, Colistin, Cimicifugic acid, Theaflavin, Silymarin and Chebulagic. We recommend further wet-lab and clinical testing of these compounds to further explore their role against SARS-CoV-2.

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The potential chemical structure of anti‐SARS‐CoV‐2 RNA‐dependent RNA polymerase

Cited by 252 publications

References 17 publications

The potential SARS-CoV-2 entry inhibitor

The potential SARS-CoV-2 entry inhibitor

Natural product-derived phytochemicals as potential agents against coronaviruses: A review

Structure based drug discovery by virtual screening of 3699 compounds against the crystal structures of six key SARS-CoV-2 proteins

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