Synthesis and anti-SARS-CoV-2 activity and mechanism research of lycorine derivatives
10.16438/j.0513-4870.2023-1121
- VernacularTitle:石蒜碱类衍生物的合成与抗SARS-CoV-2的活性和作用机制研究
- Author:
Yu-heng MEI
;
Jia-yu LI
;
Dan-qing SONG
;
Zong-gen PENG
;
Ying-hong LI
- Publication Type:Research Article
- Keywords:
lycorine derivative;
SARS-CoV-2;
RNA-dependent RNA polymerase (RdRp);
nidovirus RdRp-associated nucleotidyltransferase (NiRAN);
antivirus
- From:
Acta Pharmaceutica Sinica
2024;58(2):395-403
- CountryChina
- Language:Chinese
-
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.
