Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition

Shah Faisal, Syed Lal Badshah, Bibi Kubra, Mohamed Sharaf, Abdul-Hamid M. Emwas, Mariusz Jaremko, Mohnad Abdalla

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The 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.
Original languageEnglish (US)
Pages (from-to)223
JournalMolecules
Volume27
Issue number1
Early online dateDec 30 2021
DOIs
StatePublished - 2022

Bibliographical note

KAUST Repository Item: Exported on 2022-01-25
Acknowledgements: We appreciate King Abdullah University of Science and Technology, Saudi Arabia for their support.

ASJC Scopus subject areas

  • Organic Chemistry

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