{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:11Z","timestamp":1772138051855,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM116855"],"award-info":[{"award-number":["R01GM116855"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM138856"],"award-info":[{"award-number":["R01GM138856"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33CA225863"],"award-info":[{"award-number":["R33CA225863"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33CA246711"],"award-info":[{"award-number":["R33CA246711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>The coronavirus disease 2019 (COVID-19) pandemic has highlighted the threat of emerging respiratory viruses and has exposed the lack of availability of off-the-shelf therapeutics against new RNA viruses. Previous research has established the potential that siRNAs and RNA-targeting CRISPR have in combating known RNA viruses. However, the feasibility and tools for designing anti-viral RNA therapeutics against future RNA viruses have not yet been established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We develop the Emerging-Virus-Targeting RNA (Evitar) pipeline for designing anti-viral siRNAs and CRISPR Cas13a guide RNA (gRNA) sequences. Within Evitar, we develop Greedy Algorithm with Redundancy and Similarity-weighted Greedy Algorithm with Redundancy to enhance the performance. Time simulations using known coronavirus genomes deposited as early as 10\u2009years prior to the COVID-19 outbreak show that at least three SARS-CoV-2-targeting siRNAs are among the top 30 pre-designed siRNAs. In addition, among the top 19 pre-designed gRNAs, there are three SARS-CoV-2-targeting Cas13a gRNAs that could be predicted using information from 2011. Before-the-outbreak design is also possible against the MERS-CoV virus and the 2009-H1N1 swine flu virus. Designed siRNAs are further shown to suppress SARS-CoV-2 viral sequences using in vitro reporter assays. Our results support the utility of Evitar to pre-design anti-viral siRNAs\/gRNAs against future viruses. Therefore, we propose the development of a collection consisting of roughly 30 pre-designed, safety-tested and off-the-shelf siRNA\/CRISPR therapeutics that could accelerate responses to future RNA virus outbreaks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>Codes are available at GitHub (https:\/\/github.com\/dingyaozhang\/Evitar).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac144","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T16:18:09Z","timestamp":1647361089000},"page":"2437-2443","source":"Crossref","is-referenced-by-count":1,"title":["Evitar: designing anti-viral RNA therapies against future RNA viruses"],"prefix":"10.1093","volume":"38","author":[{"given":"Dingyao","family":"Zhang","sequence":"first","affiliation":[{"name":"Yale Stem Cell Center , Yale University, New Haven, CT 06520, USA"},{"name":"Department of Genetics, Yale University School of Medicine , New Haven, CT 06510, USA"}]},{"given":"Jingru","family":"Tian","sequence":"additional","affiliation":[{"name":"Yale Stem Cell Center , Yale University, New Haven, CT 06520, USA"},{"name":"Department of Genetics, Yale University School of Medicine , New Haven, CT 06510, USA"}]},{"given":"Yadong","family":"Wang","sequence":"additional","affiliation":[{"name":"Yale Stem Cell Center , Yale University, New Haven, CT 06520, USA"},{"name":"Department of Genetics, Yale University School of Medicine , New Haven, CT 06510, USA"},{"name":"Yale Center for RNA Science and Medicine, Yale Cancer Center , Yale University, New Haven, CT 06520, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2726-7613","authenticated-orcid":false,"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Yale Stem Cell Center , Yale University, New Haven, CT 06520, USA"},{"name":"Department of Genetics, Yale University School of Medicine , New Haven, CT 06510, USA"},{"name":"Yale Center for RNA Science and Medicine, Yale Cancer Center , Yale University, New Haven, CT 06520, USA"},{"name":"Yale Cooperative Center of Excellence in Hematology , Yale University, New Haven, CT 06520, USA"}]}],"member":"286","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"2023041402563193900_","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.cell.2020.04.020","article-title":"Development of CRISPR as an antiviral strategy to combat SARS-CoV-2 and influenza","volume":"181","author":"Abbott","year":"2020","journal-title":"Cell"},{"key":"2023041402563193900_","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.cell.2007.04.037","article-title":"Molecular basis for target RNA recognition and cleavage by human RISC","volume":"130","author":"Ameres","year":"2007","journal-title":"Cell"},{"key":"2023041402563193900_","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ddstr.2008.01.001","article-title":"Respiratory viral diseases: access to RNA interference therapy","volume":"4","author":"Bitko","year":"2007","journal-title":"Drug Discov. 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