Synthesis and anti-SARS-CoV-2 activity and mechanism research of lycorine derivatives / 药学学报
Acta Pharmaceutica Sinica
; (12): 395-403, 2024.
Article
en Zh
| WPRIM
| ID: wpr-1016657
Biblioteca responsable:
WPRO
ABSTRACT
We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC50) and selectivity index (SI) values of 2.36 μmol·L-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (KD) value of 1.36 μmol·L-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.
Texto completo:
1
Base de datos:
WPRIM
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Año:
2024
Tipo del documento:
Article
Pais de publicación:
CHINA
/
CN
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REPUBLIC OF CHINA