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