SARS-CoV-2 papain-like protease (PLpro) inhibitory and antiviral activity of small molecule derivatives for drug leads

被引：6

作者：

Ghosh, Arun K. ^{[1
,2
]}

Shahabi, Dana ^{[1
,2
]}

Imhoff, Mackenzie E. C. ^{[3
]}

Kovela, Satish ^{[1
,2
]}

Sharma, Ashish ^{[1
,2
]}

Hattori, Shin-ichiro ^{[4
]}

Higashi-Kuwata, Nobuyo ^{[4
]}

Mitsuya, Hiroaki ^{[4
,5
,6
]}

Mesecar, Andrew D. ^{[7
]}

机构：

[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

[2] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA

[3] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA

[4] Natl Ctr Global Hlth & Med, Dept Refractory Viral Dis, Shinjuku Ku, Tokyo 1628655, Japan

[5] Kumamoto Univ Hosp, Dept Clin Sci, Kumamoto 8608556, Japan

[6] Natl Canc Inst, HIV & AIDS Malignancy Branch, Expt Retrovirol Sect, Bethesda, MD 20817 USA

[7] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2023年 / 96卷

关键词：

Antiviral; Covid-19; Inhibitor; SARS-CoV-2; protease; Synthesis;

D O I：

10.1016/j.bmcl.2023.129489

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report here the synthesis and biological evaluation of a series of small molecule SARS-CoV-2 PLpro inhibitors. We compared the activity of selected compounds in both SARS-CoV-1 and SARS-CoV-2 PLpro inhibitory and antiviral assays. We have synthesized and evaluated several new structural variants of previous leads against SARS-CoV-2 PLpro. The replacement of the carboxamide functionality with sulfonamide derivatives resulted in PLpro inhibitors with potent PLpro inhibitory and antiviral activity in VeroE6 cells similar to GRL0617. To obtain molecular insight, we created an optimized model of a potent sulfonamide derivative in the SARS-CoV-2 PLpro active site.

引用

页数：6

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