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The interaction between the virus and host determines the viral infection process, including viral propagation and the disease\u2019s outcome. Understanding the interaction between the virus and host factors is a basis for unraveling the intricate biological processes in the infected cells and thereby developing more efficient and targeted antivirals. Among the various fundamental virus\u2013host interactions, autophagy plays vital and also complicated roles by directly engaging in the viral lifecycle and functioning as an anti- and\/or pro-viral factor. Autophagy thus becomes a promising target against virus infection. Since the COVID-19 pandemic, there has been an accumulation of studies aiming to investigate the roles of autophagy in SARS-CoV-2 infection by using different models and from distinct angles, providing valuable information for systematically and comprehensively dissecting the interplay between autophagy and SARS-CoV-2. In this review, we summarize the advancements in the studies of the interaction between SARS-CoV-2 and autophagy, as well as detailed molecular mechanisms. We also update the current knowledge on the pharmacological strategies used to suppress SARS-CoV-2 replication through remodeling autophagy. These extensive studies on SARS-CoV-2 and autophagy can advance our understanding of virus\u2013autophagy interaction and provide insights into developing efficient antiviral therapeutics by regulating autophagy.<\/jats:p>","DOI":"10.3390\/v16091491","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T07:38:57Z","timestamp":1726817937000},"page":"1491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Is Autophagy a Friend or Foe in SARS-CoV-2 Infection?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-7142","authenticated-orcid":false,"given":"Asifa","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, P.O. Box 582, 751 23 Uppsala, Sweden"},{"name":"Biochemistry Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-6791","authenticated-orcid":false,"given":"Jiaxin","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, P.O. Box 582, 751 23 Uppsala, Sweden"},{"name":"Zoonosis Science Center, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, P.O. 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