Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs

doi:10.3390/molecules29010225

KMS > 免疫化学研究所

	Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs
	Ren, Pengxuan1 ; Li, Shiwei1 ; Wang, Shihang1 ; Zhang, Xianglei1 ; Bai, Fang1,2,3 ; Iadarola, Paolo
	2023-12-31
发表期刊	MOLECULES (IF:4.2[JCR-2023],4.6[5-Year])
ISSN	1420-3049
EISSN	1420-3049
卷号	29 期号:1
发表状态	已发表
DOI	10.3390/molecules29010225
摘要	Human society is facing the threat of various viruses. Proteases are promising targets for the treatment of viral infections. In this study, we collected and profiled 170 protease sequences from 125 viruses that infect humans. Approximately 73 of them are viral 3-chymotrypsin-like proteases (3CL(pro)), and 11 are pepsin-like aspartic proteases (PAPs). Their sequences, structures, and substrate characteristics were carefully analyzed to identify their conserved nature for proposing a pan-3CL(pro) or pan-PAPs inhibitor design strategy. To achieve this, we used computational prediction and modeling methods to predict the binding complex structures for those 73 3CL(pro) with 4 protease inhibitors of SARS-CoV-2 and 11 protease inhibitors of HCV. Similarly, the complex structures for the 11 viral PAPs with 9 protease inhibitors of HIV were also obtained. The binding affinities between these compounds and proteins were also evaluated to assess their pan-protease inhibition via MM-GBSA. Based on the drugs targeting viral 3CL(pro) and PAPs, repositioning of the active compounds identified several potential uses for these drug molecules. As a result, Compounds 1-2, modified based on the structures of Ray1216 and Asunaprevir, indicate potential inhibition of DENV protease according to our computational simulation results. These studies offer ideas and insights for future research in the design of broad-spectrum antiviral drugs.
关键词	viral protease 3CL(pro) PAPs inhibitor design strategies drug repurposing
URL	查看原文
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS记录号	WOS:001141401700001
出版者	MDPI
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/347981
专题	免疫化学研究所信息科学与技术学院生命科学与技术学院_硕士生生命科学与技术学院_博士生免疫化学研究所_PI研究组_白芳组
通讯作者	Zhang, Xianglei; Bai, Fang
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Informat Sci & Technol, Shanghai 201210, Peoples R China 3.Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所; 信息科学与技术学院
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Ren, Pengxuan,Li, Shiwei,Wang, Shihang,et al. Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs[J]. MOLECULES,2023,29(1).
APA	Ren, Pengxuan,Li, Shiwei,Wang, Shihang,Zhang, Xianglei,Bai, Fang,&Iadarola, Paolo.(2023).Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs.MOLECULES,29(1).
MLA	Ren, Pengxuan,et al."Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs".MOLECULES 29.1(2023).