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

J 2021

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

BERA, Krishnendu; V. S. Jeba REEDA; P. R. BABILA; Dhurvas Chandrasekaran DINESH; Jozef HRITZ et. al.

Základní údaje

Originální název

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

Autoři

BERA, Krishnendu; V. S. Jeba REEDA; P. R. BABILA; Dhurvas Chandrasekaran DINESH; Jozef HRITZ a Thangavel KARTHICK

Vydání

Molecular Simulation, Taylor & Francis Ltd, 2021, 0892-7022

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.346

Kód RIV

RIV/00216224:14740/21:00122008

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1080/08927022.2021.1957884

UT WoS

000678023300001

EID Scopus

2-s2.0-85111664611

Klíčová slova anglicky

SARS-CoV-2 PLpro; SARS-CoV-2 3CLpro inhibitors; molecular docking; molecular dynamics simulation; MM/PBSA

Štítky

14313010, 143160, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 30. 1. 2024 09:41, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

LTAUSA18168, projekt VaV

Název: Selektivní NMR značení jako nástroj pro charakterizaci proteinových komplexů zapojených do neurodegenerativních onemocnění

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Selektivní NMR značení jako nástroj pro charakterizaci proteinových komplexů zapojených do neurodegenerativních onemocnění, INTER-ACTION

Citovat

BERA, Krishnendu; V. S. Jeba REEDA; P. R. BABILA; Dhurvas Chandrasekaran DINESH; Jozef HRITZ a Thangavel KARTHICK. An in silico molecular dynamics simulation study on the inhibitors of SARS-CoV-2 proteases (3CLpro and PLpro) to combat COVID-19. Molecular Simulation. Taylor & Francis Ltd, 2021, roč. 47, č. 14, s. 1168-1184. ISSN 0892-7022. Dostupné z: https://doi.org/10.1080/08927022.2021.1957884.

@article{1784137,
   author = {Bera, Krishnendu and Reeda, V. S. Jeba and Babila, P. R. and Dinesh, Dhurvas Chandrasekaran and Hritz, Jozef and Karthick, Thangavel},
   article_number = {14},
   doi = {https://doi.org/10.1080/08927022.2021.1957884},
   keywords = {SARS-CoV-2 PLpro; SARS-CoV-2 3CLpro inhibitors; molecular docking; molecular dynamics simulation; MM/PBSA},
   language = {eng},
   issn = {0892-7022},
   journal = {Molecular Simulation},
   title = {An in silico molecular dynamics simulation study on the inhibitors of SARS-CoV-2 proteases (3CLpro and PLpro) to combat COVID-19},
   url = {https://doi.org/10.1080/08927022.2021.1957884},
   volume = {47},
   year = {2021}
}

TY  - JOUR
ID  - 1784137
AU  - Bera, Krishnendu - Reeda, V. S. Jeba - Babila, P. R. - Dinesh, Dhurvas Chandrasekaran - Hritz, Jozef - Karthick, Thangavel
PY  - 2021
TI  - An in silico molecular dynamics simulation study on the inhibitors of SARS-CoV-2 proteases (3CLpro and PLpro) to combat COVID-19
JF  - Molecular Simulation
VL  - 47
IS  - 14
SP  - 1168-1184
EP  - 1168-1184
PB  - Taylor & Francis Ltd
SN  - 08927022
KW  - SARS-CoV-2 PLpro
KW  - SARS-CoV-2 3CLpro inhibitors
KW  - molecular docking
KW  - molecular dynamics simulation
KW  - MM/PBSA
UR  - https://doi.org/10.1080/08927022.2021.1957884
N2  - 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.
ER  -

BERA, Krishnendu; V. S. Jeba REEDA; P. R. BABILA; Dhurvas Chandrasekaran DINESH; Jozef HRITZ a Thangavel KARTHICK. An in silico molecular dynamics simulation study on the inhibitors of SARS-CoV-2 proteases (3CLpro and PLpro) to combat COVID-19. \textit{Molecular Simulation}. Taylor \&{} Francis Ltd, 2021, roč.~47, č.~14, s.~1168-1184. ISSN~0892-7022. Dostupné z: https://doi.org/10.1080/08927022.2021.1957884.

Přehled o publikaci