Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition
Badshah, Syed Lal
Emwas, Abdul-Hamid M.
Biological and Environmental Science and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/674286
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AbstractThe COVID-19 pandemic has caused millions of fatalities since 2019. Despite the availability of vaccines for this disease, new strains are causing rapid ailment and are a continuous threat to vaccine efficacy. Here, molecular docking and simulations identify strong inhibitors of the allosteric site of the SARS-CoV-2 virus RNA dependent RNA polymerase (RdRp). More than one hundred different flavonoids were docked with the SARS-CoV-2 RdRp allosteric site through computational screening. The three top hits were Naringoside, Myricetin and Aureusidin 4,6-diglucoside. Simulation analyses confirmed that they are in constant contact during the simulation time course and have strong association with the enzyme’s allosteric site. Absorption, distribution, metabolism, excretion and toxicity (ADMET) data provided medicinal information of these top three hits. They had good human intestinal absorption (HIA) concentrations and were non-toxic. Due to high mutation rates in the active sites of the viral enzyme, these new allosteric site inhibitors offer opportunities to drug SARS-CoV-2 RdRp. These results provide new information for the design of novel allosteric inhibitors against SARS-CoV-2 RdRp.
CitationFaisal, S., Badshah, S. L., Kubra, B., Sharaf, M., Emwas, A.-H., Jaremko, M., & Abdalla, M. (2021). Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition. Molecules, 27(1), 223. doi:10.3390/molecules27010223
SponsorsWe appreciate King Abdullah University of Science and Technology, Saudi Arabia for their support.
PubMed Central IDPMC8746673
Except where otherwise noted, this item's license is described as Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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