Extracellular Disintegration of Viral Proteins as an Innovative Strategy for Developing Broad-Spectrum Antivirals Against Coronavirus  

作　　者：Ke Sun Zhe Ding Xiaoying Jia Haonan Cheng Yingwen Li Yan Wu Zhuoyu Li Xiaohua Huang Fangxu Pu Entao Li Guiyou Wang Wei Wang Yun Ding Gary Wong Sandra Chiu Jiaming Lan Aiguo Hu 

机构地区：[1]Shanghai Key Laboratory of Advanced Polymeric Materials,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237 [2]CAS Key Laboratory of Molecular Virology&Immunology,Chinese Academy of Sciences,Shanghai 200031 [3]University of the Chinese Academy of Sciences,Beijing 100049 [4]State Key Laboratory of Virology,Center for Biosafety Mega-Science,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071 [5]Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,Anhui 230027 [6]Department of Clinical Laboratory,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,Anhui 230001

出　　处：《CCS Chemistry》2024年第2期487-496,共10页中国化学会会刊（英文）

基　　金：the National Natural Science Foundation of China(grant no.21871080);the Eastern Scholar Professorship(for A.H.);the Natural Science Foundation of Shanghai(grant no.20ZR1463900)(for J.L.).

摘　　要：The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has claimedmillions of lives and caused innumerable economic losses worldwide.Unfortunately,state-of-the-art treatments still lag behind the continual emergence of new variants.Key to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural evolution.Here,we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne(EDY)molecules.The core EDY generates reactive radical species and causes significant damage to the spike protein of coronavirus,while the hyperanion groups ensure negligible cytotoxicity of the molecules.The EDYs exhibit antiviral activity down to nanomolar concentrations,and the selectivity index of up to 20,000 against four kinds of human coronavirus,including the SARS-CoV-2 Omicron variant,suggesting the high potential of this new strategy in combating the COVID-19 pandemic and a future“disease X.”

关 键 词：ENEDIYNE broad spectrum antiviral protein disintegration coronavirus POLYANIONS 

分 类 号：R373[医药卫生—病原生物学]