Discovery of 4-((quinolin-8-ylthio)methyl)benzamide derivatives as a new class of SARS-CoV-2 nsp13 inhibitors

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL
Danchen Fan , Yuanting Huang , Rui Yao , Guo Zhang , Shengyong Yang , Linli Li
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Abstract

Antivirals have provided important protection against COVID-19, however, the emergence of SARS-CoV-2 variants and drug-resistant mutants calls for the development of novel anti-coronavirus drugs with alternative mechanisms of action. The nonstructural protein 13 (nsp13) of SARS-CoV-2 plays a conserved role in the replication of coronaviruses and has been identified as a promising target. In this study, we report a series of 4-((quinolin-8-ylthio)methyl)benzamide derivatives as inhibitors of SARS-CoV-2 nsp13. Through structure-activity relationship (SAR) analyses, we identified compound 6r, which demonstrated potent inhibition of nsp13 with an IC50 value of 0.28 ± 0.11 μM. Collectively, we discovered a new potent SARS-CoV-2 nsp13 inhibitor, which could be taken as a promising lead compound for further drug development targeting SARS-CoV-2 nsp13.

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来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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