{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:14:06Z","timestamp":1793132046341,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013278","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000}}],"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273673"],"award-info":[{"award-number":["82273673"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073581"],"award-info":[{"award-number":["82073581"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404311"],"award-info":[{"award-number":["82404311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postdoctoral Fellowship Program of CPSF","award":["GZB20230260"],"award-info":[{"award-number":["GZB20230260"]}]},{"name":"Jilin Province Science and Technology Development Plan","award":["20190304044YY"],"award-info":[{"award-number":["20190304044YY"]}]},{"name":"Jilin Province Science and Technology Development Plan","award":["20200801022 GH"],"award-info":[{"award-number":["20200801022 GH"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Crimean-Congo haemorrhagic fever virus (CCHFV) is the most prevalent tick-borne zoonotic bunyavirus, causing severe hemorrhagic fever and fatality in humans. Currently, the absence of approved vaccines or therapeutics for CCHFV infection necessitates the development of innovative therapeutic strategies. Here, we identify a guanine (G)-rich sequence located within the mRNA of the glycoprotein precursor in the medium (M) segment of the CCHFV genome, designated as M-PQS-1664(+). M-PQS-1664(+) can form stable G-quadruplex (G4) structure and functions as a negative regulatory element for viral replication. Host DDX60 is up-regulated in response to CCHFV infection, thereby it is hijacked to unwind M-PQS-1664(+) G4 for facilitating viral replication. The FDA-approved drug Cepharanthine (CEP), which competes with DDX60 to specifically stabilize M-PQS-1664(+) G4 without a global induction of host cellular G4s formation, exhibits remarkable antiviral activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . More importantly, CEP possesses antiviral activity (50% inhibitory concentration\u2009~\u20090.2 \u03bcM) that having\u2009~\u200988\u2009\u00d7\u2009the potency of ribavirin. Our findings underscore the CCHFV G4s as a promising target for drug development and highlight the significant potential of CEP in combating CCHFV.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013278","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T13:53:06Z","timestamp":1751032386000},"page":"e1013278","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Viral hijacking of host DDX60 promotes Crimean-Congo haemorrhagic fever virus replication via G-quadruplex unwinding"],"prefix":"10.1371","volume":"21","author":[{"given":"Yutong","family":"Sui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinpeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyuan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanshun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-9434","authenticated-orcid":true,"given":"Jinyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"issue":"7","key":"ppat.1013278.ref001","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41579-023-00871-9","article-title":"Crimean-Congo 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Group of the National Emerging Pathogens T, Education Center\u2019s Special Pathogens Research N","year":"2024","journal-title":"Emerg Infect Dis"},{"issue":"9","key":"ppat.1013278.ref005","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/cid\/cit527","article-title":"Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality","volume":"57","author":"B Dokuzoguz","year":"2013","journal-title":"Clin Infect Dis"},{"key":"ppat.1013278.ref006","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/jmedent\/15.4.307","article-title":"The epidemiology of tick-borne Crimean-Congo hemorrhagic fever in Asia, Europe, and Africa","volume":"15","author":"H Hoogstraal","year":"1979","journal-title":"J Med Entomol"},{"issue":"9788","key":"ppat.1013278.ref007","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0140-6736(11)60680-6","article-title":"Crimean-Congo haemorrhagic fever in 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Goubau","year":"2015","journal-title":"Eur J Immunol"},{"issue":"85","key":"ppat.1013278.ref053","doi-asserted-by":"crossref","first-page":"11913","DOI":"10.1039\/D2CC03135C","article-title":"Ligand-based drug repurposing strategy identified SARS-CoV-2 RNA G-quadruplex binders","volume":"58","author":"F Moraca","year":"2022","journal-title":"Chem Commun (Camb)"},{"issue":"13","key":"ppat.1013278.ref054","doi-asserted-by":"crossref","first-page":"5019","DOI":"10.3390\/molecules28135019","article-title":"Pharmacological Activity of Cepharanthine","volume":"28","author":"K Liu","year":"2023","journal-title":"Molecules"},{"key":"ppat.1013278.ref055","doi-asserted-by":"crossref","first-page":"107659","DOI":"10.1016\/j.pharmthera.2020.107659","article-title":"Molecular mechanisms and therapeutic implications of tetrandrine and cepharanthine in T cell acute lymphoblastic leukemia and autoimmune diseases","volume":"217","author":"W Xu","year":"2021","journal-title":"Pharmacol 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