Novel Inhibitors of SARS-CoV-2 RNA Identified through Virtual Screening.
J Chem Inf Model
; 64(15): 6190-6196, 2024 Aug 12.
Article
em En
| MEDLINE
| ID: mdl-39037082
ABSTRACT
We currently lack antivirals for most human viruses. In a quest for new molecules, focusing on viral RNA, instead of viral proteins, can represent a promising strategy. In this study, new inhibitors were identified starting from a published crystal structure of the tertiary SARS-CoV-2 RNA involved in the -1 programmed ribosomal frameshift. The pseudoknot structure was refined, and a virtual screening was performed using the repository of binders to the nucleic acid library, taking into consideration RNA flexibility. Hit compounds were validated against the wild-type virus and with a dual-luciferase assay measuring the frameshift efficiency. Several active molecules were identified. Our study reveals new inhibitors of SARS-CoV-2 but also highlights the feasibility of targeting RNA starting from virtual screening, a strategy that could be broadly applied to drug development.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
RNA Viral
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Avaliação Pré-Clínica de Medicamentos
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SARS-CoV-2
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça