Your browser doesn't support javascript.
Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition.
Faisal, Shah; Badshah, Syed Lal; Kubra, Bibi; Sharaf, Mohamed; Emwas, Abdul-Hamid; Jaremko, Mariusz; Abdalla, Mohnad.
  • Faisal S; Department of Chemistry, Islamia College University Peshawar, Peshawar 25120, Pakistan.
  • Badshah SL; Department of Chemistry, Islamia College University Peshawar, Peshawar 25120, Pakistan.
  • Kubra B; Department of Chemistry, Islamia College University Peshawar, Peshawar 25120, Pakistan.
  • Sharaf M; Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
  • Emwas AH; Department of Biochemistry, Faculty of Agriculture, AL-Azhar University, Nasr City, Cairo 11751, Egypt.
  • Jaremko M; Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
  • Abdalla M; Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Molecules ; 27(1)2021 Dec 30.
Article in English | MEDLINE | ID: covidwho-1580564
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Flavonoids / Computational Biology / Drug Evaluation, Preclinical / Coronavirus RNA-Dependent RNA Polymerase / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Traditional medicine / Vaccines Limits: Humans Language: English Journal subject: Biology Year: 2021 Document Type: Article Affiliation country: Molecules27010223

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Flavonoids / Computational Biology / Drug Evaluation, Preclinical / Coronavirus RNA-Dependent RNA Polymerase / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Traditional medicine / Vaccines Limits: Humans Language: English Journal subject: Biology Year: 2021 Document Type: Article Affiliation country: Molecules27010223