NPC1-regulated dynamic of clathrin-coated pits is essential for viral entry

查看全文 作　　者：Guoli [1,2]Li;Bingqian [1,2]Su;Pengfei [1,2]Fu;Yilin [4]Bai;Guangxu [1,2]Ding;Dahua [1,2]Li;Jiang [1,2,3]Wang;Guoyu [1,2,3]Yang;Beibei [1,2,3]Chu

机构地区：[1]College of Veterinary Medicine,Henan Agricultural University,Zhengzhou 450046,China;[2]Key Laboratory of Animal Biochemistry and Nutrition,Ministry of Agriculture and Rural Affairs of the People’s Republic of China,Zhengzhou 450046,China;[3]International Joint Research Center of National Animal Immunology,Henan Agricultural University,Zhengzhou 450046,China;[4]College of Veterinary Medicine,Northwest A&F University,Yangling 712100,China

出　　处：《Science China(Life Sciences)》索引2022年第65卷第2期,共21页

摘　　要：Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread.Therefore,the identification of lipids and metabolic pathways that are suitable targets for antiviral development is crucial.Using a library of compounds targeting host lipid metabolic factors and testing them for their ability to block pseudorabies virus(PRV)and vesicular stomatitis virus(VSV)infection,we found that U18666A,a specific inhibitor of Niemann-Pick C1(NPC1),is highly potent in suppressing the entry of diverse viruses including pseudotyped severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).NPC1 deficiency markedly attenuates viral growth by decreasing cholesterol abundance in the plasma mem-brane,thereby inhibiting the dynamics of clathrin-coated pits(CCPs),which are indispensable for clathrin-mediated endocytosis.Significantly,exogenous cholesterol can complement the dynamics of CCPs,leading to efficient viral entry and infectivity.Administration of U18666A improves the survival and pathology of PRV-and influenza A virus-infected mice.Thus,our studies demonstrate a unique mechanism by which NPC1 inhibition achieves broad antiviral activity,indicating a potential new therapeutic strategy against SARS-CoV-2,as well as other emerging viruses. 关键词：broad-spectrum antiviral NPC inhibition CCP dynamics viral entry

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NPC1-regulated dynamic of clathrin-coated pits is essential for viral entry

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