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Our studies here showing that Nsp1 selectively blocks translation of host but not viral proteins by proper coordination of its N- and C-terminal domains to advance our understanding on SARS-CoV-2 pathogenesis. Our finding that stem-loop 1, a highly conserved sequence in the SARS-CoV-2 5\u2032 UTR, is necessary and sufficient for bypassing Nsp1-mediated shutdown led to the design of antisense oligonucleotides targeting this sequence that make viral translation susceptible to Nsp1 shutdown, interfere with viral replication, and protect SARS-CoV-2\u2013infected mice. This strategy of turning SARS-CoV-2\u2019s own virulence against itself could be harnessed therapeutically.<\/jats:p>","DOI":"10.1073\/pnas.2117198119","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T16:00:48Z","timestamp":1644595248000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":111,"title":["Targeting stem-loop 1 of the SARS-CoV-2 5\u2032 UTR to suppress viral translation and Nsp1 evasion"],"prefix":"10.1073","volume":"119","author":[{"given":"Setu M.","family":"Vora","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115"},{"name":"Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Biological 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