生物技术通报2026，Vol.42Issue(2)：121-135,15.DOI:10.13560/j.cnki.biotech.bull.1985.2025-0826
宿主蛋白酶与冠状病毒入侵:从S蛋白裂解机制到蛋白酶抑制剂的开发应用
Host Proteases and Coronavirus Invasion:From S Protein Cleavage Mechanism to Development and Applications of Protease Inhibitor
摘要
Abstract
Coronaviruses,a class of RNA viruses,demonstrate a broad host range,infecting various mammals and birds.The process by which these viruses invade host cells is closely associated with the spike(S)protein.This major glycoprotein,located on the surface of the virus,consists of two subunits:S1 and S2.The S1 subunit is responsible for recognizing and binding to the host cell receptor,while the S2 subunit undergoes conformational rearrangement following cleavage by host protease.This rearrangement facilitates the fusion of the virus with cell membrane,thereby enabling invasion.Different coronaviruses feature distinct motifs on their S proteins that serve as recognition sites for various host proteases such as transmembrane serine protease 2(TMPRSS2),Furin,cathepsin L/B(CTSL/B),and trypsin.The molecular characteristics and activation mechanisms of these protease cleavage sites vary,influencing the virus's invasion routes and infection efficiency in the host cells.Variations in expressions and activities of host proteases across different tissues or cell types significantly affect the tissue tropism and transmission routes of the virus.Protease inhibitors targeting these host proteases can effectively impede virus invasion and transmission,representing a crucial focus in current anti-coronavirus drug development.This paper systematically reviews the molecular characteristics of key cleavage sites in the S proteins of various coronaviruses,investigates the activation mechanisms of distinct host proteases,and discusses the development strategies for protease inhibitors aimed at these proteases,along with their potential applications in antiviral therapy.By analyzing this critical mechanism,this review aims to offer theoretical support for a deeper comprehension of coronaviruses'pathogenic mechanisms and to provide a scientific foundation for designing and developing novel antiviral medications.关键词
冠状病毒/S蛋白/裂解位点/宿主蛋白酶/蛋白酶抑制剂Key words
coronavirus/S protein/cleavage site/host protease/protease inhibitor引用本文复制引用
姜逸,俞燕,高明燕,张笛,付立霞,程旭,陈祥,龚建森,张莹,杨亲..宿主蛋白酶与冠状病毒入侵:从S蛋白裂解机制到蛋白酶抑制剂的开发应用[J].生物技术通报,2026,42(2):121-135,15.基金项目
江苏省自然科学基金面上项目(BK20241979),江苏省人兽共患病学重点实验室资助项目(R2306) （BK20241979）
