Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion
<jats:title>Significance</jats:title> <jats:p>The COVID-19 pandemic and the ever-evolving variants of SARS-CoV-2 are taking a toll on human health. Despite the successful rollout of vaccines, effective therapies are still urgently needed. Our studies here showing that Ns...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2023
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| Online Access: | https://hdl.handle.net/1721.1/150482 |
| _version_ | 1826211599370682368 |
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| author | Vora, Setu M Fontana, Pietro Mao, Tianyang Leger, Valerie Zhang, Ying Fu, Tian-Min Lieberman, Judy Gehrke, Lee Shi, Ming Wang, Longfei Iwasaki, Akiko Wu, Hao |
| author2 | Harvard-MIT Program in Health Sciences and Technology |
| author_facet | Harvard-MIT Program in Health Sciences and Technology Vora, Setu M Fontana, Pietro Mao, Tianyang Leger, Valerie Zhang, Ying Fu, Tian-Min Lieberman, Judy Gehrke, Lee Shi, Ming Wang, Longfei Iwasaki, Akiko Wu, Hao |
| author_sort | Vora, Setu M |
| collection | MIT |
| description | <jats:title>Significance</jats:title>
<jats:p>The COVID-19 pandemic and the ever-evolving variants of SARS-CoV-2 are taking a toll on human health. Despite the successful rollout of vaccines, effective therapies are still urgently needed. 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′ 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–infected mice. This strategy of turning SARS-CoV-2’s own virulence against itself could be harnessed therapeutically.</jats:p> |
| first_indexed | 2024-09-23T15:08:32Z |
| format | Article |
| id | mit-1721.1/150482 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:08:32Z |
| publishDate | 2023 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1504822023-04-12T03:09:45Z Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion Vora, Setu M Fontana, Pietro Mao, Tianyang Leger, Valerie Zhang, Ying Fu, Tian-Min Lieberman, Judy Gehrke, Lee Shi, Ming Wang, Longfei Iwasaki, Akiko Wu, Hao Harvard-MIT Program in Health Sciences and Technology <jats:title>Significance</jats:title> <jats:p>The COVID-19 pandemic and the ever-evolving variants of SARS-CoV-2 are taking a toll on human health. Despite the successful rollout of vaccines, effective therapies are still urgently needed. 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′ 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–infected mice. This strategy of turning SARS-CoV-2’s own virulence against itself could be harnessed therapeutically.</jats:p> 2023-04-11T13:49:25Z 2023-04-11T13:49:25Z 2022 2023-04-11T13:44:26Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150482 Vora, Setu M, Fontana, Pietro, Mao, Tianyang, Leger, Valerie, Zhang, Ying et al. 2022. "Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion." Proceedings of the National Academy of Sciences of the United States of America, 119 (9). en 10.1073/PNAS.2117198119 Proceedings of the National Academy of Sciences of the United States of America Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Vora, Setu M Fontana, Pietro Mao, Tianyang Leger, Valerie Zhang, Ying Fu, Tian-Min Lieberman, Judy Gehrke, Lee Shi, Ming Wang, Longfei Iwasaki, Akiko Wu, Hao Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion |
| title | Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion |
| title_full | Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion |
| title_fullStr | Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion |
| title_full_unstemmed | Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion |
| title_short | Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion |
| title_sort | targeting stem loop 1 of the sars cov 2 5 utr to suppress viral translation and nsp1 evasion |
| url | https://hdl.handle.net/1721.1/150482 |
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