An in silico molecular dynamics simulation study on the inhibitors of SARS-CoV-2 proteases (3CLpro and PLpro) to combat COVID-19

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00544623" target="_blank" >RIV/61388963:_____/21:00544623 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/21:00122008

Result on the web

<a href="https://doi.org/10.1080/08927022.2021.1957884" target="_blank" >https://doi.org/10.1080/08927022.2021.1957884</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/08927022.2021.1957884" target="_blank" >10.1080/08927022.2021.1957884</a>

Result language

angličtina

Original language name

An in silico molecular dynamics simulation study on the inhibitors of SARS-CoV-2 proteases (3CLpro and PLpro) to combat COVID-19

Original language description

The work attempts to recognise the possible inhibitors against Papain-like protease (PLpro) and 3-Chymotrypsin-like protease (3CLpro) of SARS-CoV-2 to combat infectious COVID-19 virus using in silico studies. These two proteases are predominantly involved in the virus replication cycle, hence they are considered as potential drug targets. The virtual dock screening was performed for 53 selected drugs. The drugs with higher binding energy and oriented in the vicinity of active binding sites were selected for finding thermal stability using molecular dynamics (MD) simulation. The docking result reflects that the drugs A17 (Dasabuvir) and A34 (Methisazone) bind with PLpro and the drugs A17 and A53 (Vaniprevir) bind with 3CLpro with higher binding affinities. The MD simulation and principal component analysis show that the drug A17 has stable dynamic behaviour with both proteins over the 300 ns time-scale. The binding free energy of complexes was predicted from the last 100 ns trajectories using MM/PBSA. The predicted binding free energy of PLPro-A17 (Dasabuvir) and PLpro-A34 complexes (Methisazone) were −16.1 kcal/mol and −12.3 kcal/mol, respectively and −41.3 kcal/mol and −11.9 kcal/mol for 3CLpro-A17 (Dasabuvir) and 3CLpro-A53 (Vaniprevir) complexes, respectively. However, further experimental validation is required to confirm their inhibitory activities against SARS-CoV-2 causing COVID-19.

Czech name

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Czech description

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Type

J_imp - 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

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

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

Name of the periodical

Molecular Simulation

ISSN

0892-7022

e-ISSN

1029-0435

Volume of the periodical

47

Issue of the periodical within the volume

14

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

1168-1184

UT code for WoS article

000678023300001

EID of the result in the Scopus database

2-s2.0-85111664611