{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:24:24Z","timestamp":1791260664426,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Department of Defense Award","award":["W81XWH2110029"],"award-info":[{"award-number":["W81XWH2110029"]}]},{"name":"a Ferring COVID-19 Investigational Grant to C.-W.C.","award":["W81XWH2110029"],"award-info":[{"award-number":["W81XWH2110029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, causing surges, breakthrough infections, and devastating losses\u2014underscoring the importance of identifying SARS-CoV-2 antivirals. A simple, accessible human cell culture model permissive to SARS-CoV-2 variants is critical for identifying and assessing antivirals in a high-throughput manner. Although human alveolar A549 cells are a valuable model for studying respiratory virus infections, they lack two essential host factors for SARS-CoV-2 infection: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). SARS-CoV-2 uses the ACE2 receptor for viral entry and TMPRSS2 to prime the SARS-CoV-2 spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a suitable human cell line for SARS-CoV-2 studies by transducing human ACE2 and TMPRSS2 into A549 cells. We show that subclones highly expressing ACE2 and TMPRSS2 (\u201cACE2plus\u201d and the subclone \u201cACE2plusC3\u201d) are susceptible to infection with SARS-CoV-2, including the delta and omicron variants. These subclones express more ACE2 and TMPRSS2 transcripts than existing commercial A549 cells engineered to express ACE2 and TMPRSS2. Additionally, the antiviral drugs EIDD-1931, remdesivir, nirmatrelvir, and nelfinavir strongly inhibit SARS-CoV-2 variants in our infection model. Our data show that ACE2plusC3 cells are highly permissive to SARS-CoV-2 infection and can be used to identify anti-SARS-CoV-2 drugs.<\/jats:p>","DOI":"10.3390\/v14071369","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T22:43:00Z","timestamp":1656024180000},"page":"1369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["A Newly Engineered A549 Cell Line Expressing ACE2 and TMPRSS2 Is Highly Permissive to SARS-CoV-2, Including the Delta and Omicron Variants"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6914-4681","authenticated-orcid":false,"given":"Ching-Wen","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6002-3816","authenticated-orcid":false,"given":"Krishna","family":"Parsi","sequence":"additional","affiliation":[{"name":"Diabetes Center of Excellence and Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Somasundaran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Vanderleeden","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1309-570X","authenticated-orcid":false,"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Cousineau","sequence":"additional","affiliation":[{"name":"Diabetes Center of Excellence and Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Finberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Kurt-Jones","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12992-022-00827-3","article-title":"Predicting the number of COVID-19 infections and deaths in USA","volume":"18","author":"Ebubeogu","year":"2022","journal-title":"Global Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100618","DOI":"10.1016\/j.cpcardiol.2020.100618","article-title":"COVID-19 and Multiorgan Response","volume":"45","author":"Zaim","year":"2020","journal-title":"Curr. 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