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Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus

Signal Transduction and Targeted Therapy 2022年第11期7卷 4223-4234页

作者： Yeong-Bin Baek Hyung-Jun Kwon Muhammad Sharif jeongah lim In-Chul Lee Young Bae Ryu Jae-In Lee Ji-Sun Kim Young-Seung Lee Dong-Hoon Kim Sang-Ik Park Don-Kyu Kim Jeong-Sun Kim Hyon EChoy Sunwoo Lee Hueng-Sik Choi Timothy FOsborne Tae-Il Jeon Kyoung-Oh Cho Laboratory of Veterinary Pathology College of Veterinary MedicineChonnam National UniversityGwangju61186Republic of Korea Functional Biomaterial Research Center Korea Research Institute of Bioscience&BiotechnologyJeongeup-siJeollabuk-do56212Republic of Korea Department of Chemistry Chonnam National UniversityGwangju61186Republic of Korea Korean Collection for Type Cultures Korea Research Institute of Bioscience&BiotechnologyJeongeup-siJeollabuk-do56212Republic of Korea Department of Animal Science Chonnam National UniversityGwangju61186Republic of Korea Department of Pharmacology Korea University College of MedicineSeoul02841Republic of Korea Department of Integrative Food Bioscience and BiotechnologyChonnam National UniversityGwangju61186Republic of Korea Department of Microbiology Chonnam National University Medical SchoolGwangju61486Republic of Korea School of Biological Sciences and Technology Chonnam National UniversityGwangju61186Republic of Korea Institute for Fundamental Biomedical Research Department of Medicine and Biological ChemistryJohns Hopkins University School of MedicineSt.PetersburgFL33701USA

The biosynthesis of host lipids and/or lipid droplets(LDs)has been studied extensively as a putative therapeutic target in diverse viral ***,directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely ***,we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids(FFAs)at the late stage of diverse RNA viral infections,which represents a broad-spectrum antiviral *** of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection,thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of *** replication of SARS-CoV-2 and influenza A virus(IAV),which is suppressed by the treatment with LD-associated lipases inhibitors,is rescued by supplementation with *** administration of lipase inhibitors,either individually or in a combination with virus-targeting drugs,protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected ***,the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2-and IAV-challenged animals,a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV *** conclusion,the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19-and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.

关键词： linkage furthermore thereby

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