{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:45:54Z","timestamp":1790138754126,"version":"4.0.1"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bavarian State Government"},{"name":"Else Kroener-Research College"},{"DOI":"10.13039\/501100001663","name":"Volkswagen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"ERC","doi-asserted-by":"publisher","award":["ERC-StG 637830"],"award-info":[{"award-number":["ERC-StG 637830"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"ERC","doi-asserted-by":"publisher","award":["817798"],"award-info":[{"award-number":["817798"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["PI1084\/5"],"award-info":[{"award-number":["PI1084\/5"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["TRR178\/TP11"],"award-info":[{"award-number":["TRR178\/TP11"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["TRR 237\/A07"],"award-info":[{"award-number":["TRR 237\/A07"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Federal Ministry of Education and Research"},{"DOI":"10.13039\/501100001655","name":"German Academic Exchange Service","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A promising approach to tackle the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) could be small interfering (si)RNAs. So far it is unclear, which viral replication steps can be efficiently inhibited with siRNAs. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, and thereby terminate replication before start of transcription and prevent virus-induced cell death. Coronaviruses replicate via negative sense RNA intermediates using a unique discontinuous transcription process. As a result, each viral RNA contains identical sequences at the 5\u2032 and 3\u2032 end. Surprisingly, siRNAs were not active against intermediate negative sense transcripts. Targeting common sequences shared by all viral transcripts allowed simultaneous suppression of gRNA and subgenomic (sg)RNAs by a single siRNA. The most effective suppression of viral replication and spread, however, was achieved by siRNAs that targeted open reading frame 1 (ORF1) which only exists in gRNA. In contrast, siRNAs that targeted the common regions of transcripts were outcompeted by the highly abundant sgRNAs leading to an impaired antiviral efficacy. Verifying the translational relevance of these findings, we show that a chemically modified siRNA that targets a highly conserved region of ORF1, inhibited SARS-CoV-2 replication ex vivo in explants of the human lung. Our work encourages the development of siRNA-based therapies for COVID-19 and suggests\u00a0that early therapy start, or prophylactic application, together with specifically targeting gRNA, might be key for high antiviral efficacy.<\/jats:p>","DOI":"10.1093\/nar\/gkab1248","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T12:06:36Z","timestamp":1638705996000},"page":"333-349","source":"Crossref","is-referenced-by-count":61,"title":["Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread"],"prefix":"10.1093","volume":"50","author":[{"given":"Shubhankar","family":"Ambike","sequence":"first","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cho-Chin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Feuerherd","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stoyan","family":"Velkov","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domizia","family":"Baldassi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Butenandtstra\u00dfe 5, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suliman Qadir","family":"Afridi","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Porras-Gonzalez","sequence":"additional","affiliation":[{"name":"Institute of Lung Biology and Disease (ILBD) and Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Zentrum M\u00fcnchen, Member of the German Center for Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Lung Biology and Disease (ILBD) and Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Zentrum M\u00fcnchen, Member of the German Center for Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Hagen","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Kneidinger","sequence":"additional","affiliation":[{"name":"Department of Medicine V, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mircea\u00a0Gabriel","family":"Stoleriu","sequence":"additional","affiliation":[{"name":"Center for Thoracic Surgery Munich, Ludwig-Maximilians-University of Munich (LMU) and Asklepios Pulmonary Hospital; Marchioninistra\u00dfe 15, 81377 Munich and Robert-Koch-Allee 2, 82131 Gauting, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Grass","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Burgstaller","sequence":"additional","affiliation":[{"name":"Institute of Lung Biology and Disease (ILBD) and Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Zentrum M\u00fcnchen, Member of the German Center for Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pichlmair","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich partner site, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia\u00a0M","family":"Merkel","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Butenandtstra\u00dfe 5, 81377 Munich, Germany"},{"name":"Institute of Lung Biology and Disease (ILBD) and Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Zentrum M\u00fcnchen, Member of the German Center for Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunkyu","family":"Ko","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"},{"name":"Infectious Diseases Therapeutic Research Center, Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), 34114 Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Michler","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technische Universit\u00e4t M\u00fcnchen \/ Helmholtz Zentrum M\u00fcnchen, Trogerstr. 30, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich partner site, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"2022011223484506800_B1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","article-title":"Virological assessment of hospitalized patients with COVID-2019","volume":"581","author":"W\u00f6lfel","year":"2020","journal-title":"Nature"},{"key":"2022011223484506800_B2","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41591-020-0868-6","article-title":"SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes","volume":"26","author":"Sungnak","year":"2020","journal-title":"Nat. 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