Virtual screening and activity study of antiviral compounds targeting inosine 5′-monophosphate dehydrogenase
10.16438/j.0513-4870.2022-0644
- VernacularTitle:以次黄嘌呤脱氢酶为靶点的抗病毒化合物的虚拟筛选及活性研究
- Author:
Shi-bo KOU
;
Rong-mei GAO
;
Hong YI
;
Lian-qi SUN
;
Yu-huan LI
;
Zhuo-rong LI
- Publication Type:Research Article
- Keywords:
inosine 5′-monophosphate dehydrogenase;
inhibitor;
molecular docking;
coronavirus;
activity screening
- From:
Acta Pharmaceutica Sinica
2022;57(10):3011-3018
- CountryChina
- Language:Chinese
-
Abstract:
Inosine 5′-monophosphate dehydrogenase (IMPDH) is a key enzyme catalyzing the rate-limiting step of de novo nucleotide synthesis in vivo. In recent years, it has become a therapeutic target for anti-virus, anti-bacterial, anti-cancer, anti-parasitic and other diseases. IMPDH inhibitors have been shown to inhibit viral prolife-ration in host cells by depleting guanosine 5′-monophosphate (GMP), the raw material required for viral replication in host cells, with broad-spectrum antiviral properties. In order to find novel anti-coronavirus drugs, this study screened 22 potential IMPDH inhibitors from 70 000 natural small molecule libraries based on IMPDH protein structure using molecular docking and ROC calculation for virtual screening. With ribavirin as the positive control drug, Huh7 cell and H460 cell models were used to verify the anti-coronavirus HCoV-229E and HCoV-OC43 activities of 22 selected target compounds. Among them, compounds 11, 12, 15 and 16 showed inhibitory activity against coronavirus HCoV-229E. The compounds 4, 12, 13 and 15 showed inhibitory activities against coronavirus HCoV-OC43. 12 and 15 showed significant inhibitory activity against both two coronaviruses, and their efficacy was similar to ribavirin at the same dose, which can be further studied as a lead compound for IMPDH inhibitors.
