{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:25:11Z","timestamp":1790727911856,"version":"4.1.0"},"reference-count":178,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The COVID-19 pandemic is caused by the 2019\u2013nCoV\/SARS-CoV-2 virus. This severe acute respiratory syndrome is currently a global health emergency and needs much effort to generate an urgent practical treatment to reduce COVID-19 complications and mortality in humans. Viral infection activates various cellular responses in infected cells, including cellular stress responses such as unfolded protein response (UPR) and autophagy, following the inhibition of mTOR. Both UPR and autophagy mechanisms are involved in cellular and tissue homeostasis, apoptosis, innate immunity modulation, and clearance of pathogens such as viral particles. However, during an evolutionary arms race, viruses gain the ability to subvert autophagy and UPR for their benefit. SARS-CoV-2 can enter host cells through binding to cell surface receptors, including angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1). ACE2 blockage increases autophagy through mTOR inhibition, leading to gastrointestinal complications during SARS-CoV-2 virus infection. NRP1 is also regulated by the mTOR pathway. An increased NRP1 can enhance the susceptibility of immune system dendritic cells (DCs) to SARS-CoV-2 and induce cytokine storm, which is related to high COVID-19 mortality. Therefore, signaling pathways such as mTOR, UPR, and autophagy may be potential therapeutic targets for COVID-19. Hence, extensive investigations are required to confirm these potentials. Since there is currently no specific treatment for COVID-19 infection, we sought to review and discuss the important roles of autophagy, UPR, and mTOR mechanisms in the regulation of cellular responses to coronavirus infection to help identify new antiviral modalities against SARS-CoV-2 virus.<\/jats:p>","DOI":"10.3390\/ijms22115992","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T15:58:44Z","timestamp":1622563124000},"page":"5992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Autophagy, Unfolded Protein Response, and Neuropilin-1 Cross-Talk in SARS-CoV-2 Infection: What Can Be Learned from Other Coronaviruses"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5556-2102","authenticated-orcid":false,"given":"Morvarid","family":"Siri","sequence":"first","affiliation":[{"name":"Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8553-9221","authenticated-orcid":false,"given":"Sanaz","family":"Dastghaib","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7856-6029","authenticated-orcid":false,"given":"Mozhdeh","family":"Zamani","sequence":"additional","affiliation":[{"name":"Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3004-6283","authenticated-orcid":false,"given":"Nasim","family":"Rahmani-Kukia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4366-6764","authenticated-orcid":false,"given":"Kiarash Roustai","family":"Geraylow","sequence":"additional","affiliation":[{"name":"Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799422, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shima","family":"Fakher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Keshvarzi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-9228","authenticated-orcid":false,"given":"Parvaneh","family":"Mehrbod","sequence":"additional","affiliation":[{"name":"Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran 1316943551, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9969-170X","authenticated-orcid":false,"given":"Mazaher","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838695, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-0473","authenticated-orcid":false,"given":"Pooneh","family":"Mokarram","sequence":"additional","affiliation":[{"name":"Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"},{"name":"Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Coombs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-508X","authenticated-orcid":false,"given":"Saeid","family":"Ghavami","sequence":"additional","affiliation":[{"name":"Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran"},{"name":"Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Faculty of Medicine, Katowice School of Technology, 40-555 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1128\/9781555818432.ch6","article-title":"RNA Viruses: A Case Study of the Biology of Emerging Infectious Diseases","volume":"1","author":"Woolhouse","year":"2014","journal-title":"One Health People Anim. 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