Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach
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ORIGINAL ARTICLE
Hordatines as a Potential Inhibitor of COVID‑19 Main Protease and RNA Polymerase: An In‑Silico Approach Mohammed A. Dahab1 · Mostafa M. Hegazy2 · Hatem S. Abbass2,3 Received: 19 July 2020 / Accepted: 14 October 2020 © The Author(s) 2020
Abstract Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID19). The key targets of COVID-19, protease (PDB ID: 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. We used 3 different conformations of protease target (6M0K, 6Y2F and 7BQY) and two different score functions to strengthen the probability of inhibitors discovery. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or both COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of both targets. The top 7 hits are, flacourticin (3), sagerinic acid (16), hordatine A (23), hordatine B (24), N-feruloyl tyramine dimer (25), bisavenanthramides B-5 (29) and vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13659-020-00275-9) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article
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Graphic Abstract
Keywords Barley · COVID-19 · Docking · Hordatine · Protease · RNA polymerase · MOE
1 Introduction During the last coronavirus outbreak, the rapid development of computer-aided drug discovery used for the in silico molecular modelling along with natural product databases have dramatically improved the drug development process. The inhibition of viral replication is a good strategy for antiviral drug discovery and development [1]. SARS-CoV replicase gene has been revealed to encode a number of enzymatic functions. These include RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), a papainlike protease (PLpro) and a helicase. [2] 3C-like protease (3CLpro) and RNA polymerase play an important role in the replication of the virus and has a highly conserved catalytic domain from the SARS virus which
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