Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00539587" target="_blank" >RIV/61388963:_____/21:00539587 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.3389/fchem.2020.595273" target="_blank" >https://doi.org/10.3389/fchem.2020.595273</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fchem.2020.595273" target="_blank" >10.3389/fchem.2020.595273</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease

Popis výsledku v původním jazyce

The recent pandemic outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raised global health and economic concerns. Phylogenetically, SARS-CoV-2 is closely related to SARS-CoV, and both encode the enzyme main protease (Mpro/3CLpro), which can be a potential target inhibiting viral replication. Through this work, we have compiled the structural aspects of Mpro conformational changes, with molecular modeling and 1-μs MD simulations. Long-scale MD simulation resolves the mechanism role of crucial amino acids involved in protein stability, followed by ensemble docking which provides potential compounds from the Traditional Chinese Medicine (TCM) database. These lead compounds directly interact with active site residues (His41, Gly143, and Cys145) of Mpro, which plays a crucial role in the enzymatic activity. Through the binding mode analysis in the S1, S1′, S2, and S4 binding subsites, screened compounds may be functional for the distortion of the oxyanion hole in the reaction mechanism, and it may lead to the inhibition of Mpro in SARS-CoV-2. The hit compounds are naturally occurring compounds, they provide a sustainable and readily available option for medical treatment in humans infected by SARS-CoV-2. Henceforth, extensive analysis through molecular modeling approaches explained that the proposed molecules might be promising SARS-CoV-2 inhibitors for the inhibition of COVID-19, subjected to experimental validation.

Název v anglickém jazyce

Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease

Popis výsledku anglicky

The recent pandemic outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raised global health and economic concerns. Phylogenetically, SARS-CoV-2 is closely related to SARS-CoV, and both encode the enzyme main protease (Mpro/3CLpro), which can be a potential target inhibiting viral replication. Through this work, we have compiled the structural aspects of Mpro conformational changes, with molecular modeling and 1-μs MD simulations. Long-scale MD simulation resolves the mechanism role of crucial amino acids involved in protein stability, followed by ensemble docking which provides potential compounds from the Traditional Chinese Medicine (TCM) database. These lead compounds directly interact with active site residues (His41, Gly143, and Cys145) of Mpro, which plays a crucial role in the enzymatic activity. Through the binding mode analysis in the S1, S1′, S2, and S4 binding subsites, screened compounds may be functional for the distortion of the oxyanion hole in the reaction mechanism, and it may lead to the inhibition of Mpro in SARS-CoV-2. The hit compounds are naturally occurring compounds, they provide a sustainable and readily available option for medical treatment in humans infected by SARS-CoV-2. Henceforth, extensive analysis through molecular modeling approaches explained that the proposed molecules might be promising SARS-CoV-2 inhibitors for the inhibition of COVID-19, subjected to experimental validation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Chemistry

ISSN

2296-2646

e-ISSN

2296-2646

Svazek periodika

8

Číslo periodika v rámci svazku

Jan 13

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

15

Strana od-do

595273

Kód UT WoS článku

000612010100001

EID výsledku v databázi Scopus

2-s2.0-85100261875