Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemical biology for drugging undruggable targets</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Chemistry
ISSN
2296-2646
e-ISSN
2296-2646
Volume of the periodical
8
Issue of the periodical within the volume
Jan 13
Country of publishing house
CH - SWITZERLAND
Number of pages
15
Pages from-to
595273
UT code for WoS article
000612010100001
EID of the result in the Scopus database
2-s2.0-85100261875