{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:32:11Z","timestamp":1778851931772,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010423","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000}}],"reference-count":156,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031A602A"],"award-info":[{"award-number":["031A602A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KA 2989\/13-1"],"award-info":[{"award-number":["KA 2989\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000015","name":"US Department of Energy","doi-asserted-by":"crossref","award":["89233218CNA000001"],"award-info":[{"award-number":["89233218CNA000001"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Health","award":["R01-AI078881, and R01-AI116868"],"award-info":[{"award-number":["R01-AI078881, and R01-AI116868"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called \u201creplication factories\u201d), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA synthesis. In the current study, we investigate pan-viral similarities and virus-specific differences in the life cycle of this highly relevant group of viruses. We first measured the kinetics of viral RNA, viral protein, and infectious virus particle production of hepatitis C virus (HCV), dengue virus (DENV), and coxsackievirus B3 (CVB3) in the immuno-compromised Huh7 cell line and thus without perturbations by an intrinsic immune response. Based on these measurements, we developed a detailed mathematical model of the replication of HCV, DENV, and CVB3 and showed that only small virus-specific changes in the model were necessary to describe the\n                    <jats:italic>in vitro<\/jats:italic>\n                    dynamics of the different viruses. Our model correctly predicted virus-specific mechanisms such as host cell translation shut off and different kinetics of replication organelles. Further, our model suggests that the ability to suppress or shut down host cell mRNA translation may be a key factor for\n                    <jats:italic>in vitro<\/jats:italic>\n                    replication efficiency, which may determine acute self-limited or chronic infection. We further analyzed potential broad-spectrum antiviral treatment options\n                    <jats:italic>in silico<\/jats:italic>\n                    and found that targeting viral RNA translation, such as polyprotein cleavage and viral RNA synthesis, may be the most promising drug targets for all plus-strand RNA viruses. Moreover, we found that targeting only the formation of replicase complexes did not stop the\n                    <jats:italic>in vitro<\/jats:italic>\n                    viral replication early in infection, while inhibiting intracellular trafficking processes may even lead to amplified viral growth.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010423","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T14:01:55Z","timestamp":1680616915000},"page":"e1010423","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies"],"prefix":"10.1371","volume":"19","author":[{"given":"Carolin","family":"Zitzmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-3099","authenticated-orcid":true,"given":"Christopher","family":"D\u00e4chert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilde","family":"van der Schaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn","family":"van Hemert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-0002","authenticated-orcid":true,"given":"Alan S.","family":"Perelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J. M.","family":"van Kuppeveld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Bartenschlager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Binder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-2294","authenticated-orcid":true,"given":"Lars","family":"Kaderali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"pcbi.1010423.ref001","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000507423","article-title":"COVID-19 outbreak: An overview.","volume":"64","author":"M Ciotti","year":"2020","journal-title":"Chemotherapy"},{"key":"pcbi.1010423.ref002","first-page":"1","article-title":"WHO coronavirus (COVID-19) dashboard with vaccination data.","author":"World Health Organization","year":"2021","journal-title":"In: WHO [Internet]."},{"key":"pcbi.1010423.ref003","first-page":"1495","article-title":"The COVID-19 pandemic and the $16 trillion virus.","volume-title":"JAMA\u2014Journal of the American Medical Association.","author":"DM Cutler","year":"2020"},{"key":"pcbi.1010423.ref004","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S1473-3099(16)00146-8","article-title":"The global economic burden of dengue: a systematic analysis","volume":"16","author":"DS Shepard","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"pcbi.1010423.ref005","article-title":"A socio-economic impact assessment of the Zika virus in Latin America and the Caribbean.","author":"United Nations","year":"2017"},{"key":"pcbi.1010423.ref006","doi-asserted-by":"crossref","first-page":"100001","DOI":"10.1016\/j.jve.2020.06.001","article-title":"Price of a hepatitis C cure: Cost of production and current prices for direct-acting antivirals in 50 countries.","volume":"6","author":"MJ Barber","year":"2020","journal-title":"J Virus Erad."},{"key":"pcbi.1010423.ref007","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.jval.2020.03.021","article-title":"Spending on hepatitis C antivirals in the United States and Canada, 2014 to 2018.","volume":"23","author":"A Shakeri","year":"2020","journal-title":"Value in Health"},{"key":"pcbi.1010423.ref008","first-page":"1","article-title":"Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of COVID-19.","author":"FDA","year":"2021","journal-title":"In: Food and Drug Administration [Internet]."},{"key":"pcbi.1010423.ref009","article-title":"Road to elimination of HCV: Clinical challenges in HCV management.","volume-title":"Liver International.","author":"CN Hayes","year":"2022"},{"key":"pcbi.1010423.ref010","author":"World Health Organization","year":"2019","journal-title":"Hepatitis C"},{"key":"pcbi.1010423.ref011","article-title":"Dengue and severe dengue","author":"World Health Organization","year":"2016"},{"key":"pcbi.1010423.ref012","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.virusres.2015.09.013","article-title":"High-throughput approaches to unravel hepatitis C virus-host interactions","volume":"218","author":"CC Colpitts","year":"2016","journal-title":"Virus Res"},{"key":"pcbi.1010423.ref013","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1038\/s41598-017-04993-y","article-title":"Revealing enterovirus infection in chronic human disorders: An integrated diagnostic approach.","volume":"7","author":"A Genoni","year":"2017","journal-title":"Sci Rep"},{"key":"pcbi.1010423.ref014","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41579-018-0005-4","article-title":"The life cycle of non-polio enteroviruses and how to target it. 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