Applying the bioisosterism strategy to obtain lead compounds against SARS-CoV-2 cysteine proteases: An in-silico approach.
J Comput Chem
; 45(1): 35-46, 2024 01 05.
Article
em En
| MEDLINE
| ID: mdl-37641955
ABSTRACT
SARS-CoV-2 cysteine proteases are essential nonstructural proteins due to their role in the formation of the virus multiple enzyme replication-transcription complex. As a result, those functional proteins are extremely relevant targets in the development of a new drug candidate to fight COVID-19. Based on this fact and guided by the bioisosterism strategy, the present work has selected 126 out of 1050 ligands from DrugBank website. Subsequently, 831 chemical analogs containing bioisosteres, some of which became structurally simplified, were created using the MB-Isoster software, and molecular docking simulations were performed using AutoDock Vina. Finally, a study of physicochemical properties, along with pharmacokinetic profiles, was carried out through SwissADME and ADMETlab 2.0 platforms. The promising results obtained with the molecules encoded as DB00549_BI_005, DB04868_BI_003, DB11984_BI_002, DB12364_BI_006 and DB12805_BI_004 must be confirmed by molecular dynamics studies, followed by in vitro and in vivo empirical tests that ratify the advocated in-silico results.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cisteína Proteases
/
COVID-19
Limite:
Humans
Idioma:
En
Revista:
J Comput Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos