A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity  

作　　者：Yin-yan Li Guo-dong Liang Zhi-xuan Chen Ke Zhang Jin-long Liang Lin-rui Jiang Si-zu Yang Feng Jiang Shu-wen Liu Jie Yang 

机构地区：[1]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism,Guangdong Provincial Key Laboratory of New Drug Screening,Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,510515,China [2]Key Laboratory for Candidate Drug Design and Screening Based on Chemical Biology,College of Pharmacy,Inner Mongolia Medical University,Huhhot,010110,China [3]Key Laboratory of Microbio and Infectious Disease Prevention&Control in Guizhou Province/Institute of Virology,School of Basic Medicine,Guizhou Medical University,Guiyang,561113,China

出　　处：《Acta Pharmacologica Sinica》2024年第11期2380-2393,共14页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China(Grant numbers 82073897,82373915);the Science and Technology Innovation Project of Guangdong Medical Products Administration(Grant numbers S2021ZDZ042).

摘　　要：Influenza A virus(IAV)is a widespread pathogen that poses a significant threat to human health,causing pandemics with high mortality and pathogenicity.Given the emergence of increasingly drug-resistant strains of IAV,currently available antiviral drugs have been reported to be inadequate to meet clinical demands.Therefore,continuous exploration of safe,effective and broad-spectrum antiviral medications is urgently required.Here,we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo.Moreover,J1 exhibits broad-spectrum antiviral activity against enveloped viruses,including IAV,respiratory syncytial virus(RSV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),human coronavirus OC43(HCoV-OC43),herpes simplex virus type 1(HSV-1)and HSV-2.In this study,we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro.The results showed that J1 inhibited infection by IAV strains,including H1N1,H7N9,H5N1 and H3N2,as well as by oseltamivir-resistant strains.Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit,thereby blocking membrane fusion.BALB/c mice were used to establish a model of acute lung injury(ALI)induced by IAV.Treatment with J1 increased survival rates and reduced viral titers,lung index and lung inflammatory damage in virus-infected mice.In conclusion,J1 possesses significant anti-IAV effects in vitro and in vivo,providing insights into the development of broad-spectrum antivirals against future pandemics.

关 键 词：small molecule compound antiviral activity influenza A virus HEMAGGLUTININ entry inhibitor 

分 类 号：R511.7[医药卫生—内科学]