{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:54:20Z","timestamp":1790484860321,"version":"4.1.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32072866 and U20A2060"],"award-info":[{"award-number":["32072866 and U20A2060"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Viral infections usually induce the rearrangement of cellular cytoskeletal proteins and organelle membrane structures, thus creating independent compartments [termed replication organelles (ROs)] to facilitate viral genome replication. Within the ROs, viral replicases, including polymerases, helicases, and ligases, play functional roles during viral replication. These viral replicases are pivotal in the virus life cycle, and numerous studies have demonstrated that the viral replicases could be the potential targets for drugs development. Here, we summarize primarily the key replicases within viral ROs and emphasize the advancements of antiviral drugs targeting crucial viral replicases, providing novel insights into the future development of antiviral strategies.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1450060","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T05:08:49Z","timestamp":1722402529000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Viral replication organelles: the highly complex and programmed replication machinery"],"prefix":"10.3389","volume":"15","author":[{"given":"Hao","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian-Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Ji","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e00221","DOI":"10.1128\/mBio.00221-18","article-title":"Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease","volume":"9","author":"Agostini","year":"2018","journal-title":"MBio"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1126\/science.1259210","article-title":"Viral replication. 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Pharmacokinet."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/0092-8674(92)90445-i","article-title":"Three-dimensional structure of the beta subunit of E. coli DNA polymerase III holoenzyme: a sliding DNA clamp","volume":"69","author":"Kong","year":"1992","journal-title":"Cell"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"CD015219","DOI":"10.1002\/14651858.CD015219.pub2","article-title":"Favipiravir for treating COVID-19","volume":"2024","author":"Korula","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"2698","DOI":"10.1038\/s41467-023-38377-w","article-title":"Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles","volume":"14","author":"Lan","year":"2023","journal-title":"Nat. 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Biol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/s41594-023-01142-0","article-title":"Structural insight into the assembly and working mechanism of helicase-primase D5 from Mpox virus","volume":"31","author":"Li","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.3389\/fmicb.2018.02483","article-title":"Identification of amino acids essential for viral replication in the HCMV helicase-primase complex","volume":"9","author":"Ligat","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1093\/nar\/gkt1032","article-title":"Efficient DNA ligation in DNA-RNA hybrid helices by Chlorella virus DNA ligase","volume":"42","author":"Lohman","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1016\/j.cell.2021.02.013","article-title":"Antivirals with common targets against highly pathogenic viruses","volume":"184","author":"Lu","year":"2021","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"46094","DOI":"10.1074\/jbc.C100349200","article-title":"Hepatitis C virus RNA-dependent RNA polymerase (NS5B) as a mediator of the antiviral activity of ribavirin","volume":"276","author":"Maag","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.3390\/ijms23073431","article-title":"40 years after the registration of acyclovir: do we need new anti-herpetic drugs?","volume":"23","author":"Majewska","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1006\/jmbi.1999.3511","article-title":"Crystal structure of the DNA polymerase processivity factor of T4 bacteriophage","volume":"296","author":"Moarefi","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.3390\/v13061060","article-title":"Membrane-associated flavivirus replication complex-its organization and regulation","volume":"13","author":"Morita","year":"2021","journal-title":"Viruses"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"a010199","DOI":"10.1101\/cshperspect.a010199","article-title":"Poxvirus DNA replication","volume":"5","author":"Moss","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"12589","DOI":"10.1128\/JVI.01394-10","article-title":"Tetrameric ring formation of Epstein-Barr virus polymerase processivity factor is crucial for viral replication","volume":"84","author":"Nakayama","year":"2010","journal-title":"J. Virol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1016\/j.molcel.2023.06.023","article-title":"Structures of dengue virus RNA replicase complexes","volume":"83","author":"Osawa","year":"2023","journal-title":"Mol. Cell"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.3390\/v13102015","article-title":"HSV-1 DNA replication-coordinated regulation by viral and cellular factors","volume":"13","author":"Packard","year":"2021","journal-title":"Viruses"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"e0087823","DOI":"10.1128\/jvi.00878-23","article-title":"Identification of host dependency factors involved in SARS-CoV-2 replication organelle formation through proteomics and ultrastructural analysis","volume":"97","author":"Pahmeier","year":"2023","journal-title":"J. Virol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"JC4","DOI":"10.7326\/ACPJ202007210-005","article-title":"Remdesivir improved time to recovery in adults hospitalized with COVID-19 and lower respiratory tract involvement","volume":"173","author":"Paladugu","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"100080","DOI":"10.1016\/j.xinn.2021.100080","article-title":"Structural basis of SARS-CoV-2 polymerase inhibition by favipiravir","volume":"2","author":"Peng","year":"2021","journal-title":"Innovation (Camb)"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"107774","DOI":"10.1016\/j.celrep.2020.107774","article-title":"Structural and biochemical characterization of the nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2","volume":"31","author":"Peng","year":"2020","journal-title":"Cell Rep."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1126\/science.ade6360","article-title":"Structure of monkeypox virus DNA polymerase holoenzyme","volume":"379","author":"Peng","year":"","journal-title":"Science"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/s41586-023-06608-1","article-title":"Molecular mechanism of de novo replication by the Ebola virus polymerase","volume":"622","author":"Peng","year":"","journal-title":"Nature"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"5695","DOI":"10.3390\/molecules25235695","article-title":"Targeting the RdRp of emerging RNA viruses: the structure-based drug design challenge","volume":"25","author":"Picarazzi","year":"2020","journal-title":"Molecules"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"e1005893","DOI":"10.1371\/journal.ppat.1005893","article-title":"DNA polymerase \u03ba is a key cellular factor for the formation of covalently closed circular DNA of hepatitis B virus","volume":"12","author":"Qi","year":"2016","journal-title":"PLoS Pathog."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/s41586-022-04835-6","article-title":"The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle","volume":"606","author":"Ricciardi","year":"2022","journal-title":"Nature"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"13314","DOI":"10.1074\/jbc.M111.226191","article-title":"Functional dissection of the DNA interface of the nucleotidyltransferase domain of chlorella virus DNA ligase","volume":"286","author":"Samai","year":"","journal-title":"J. Biol. Chem."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"22642","DOI":"10.1074\/jbc.M111.245399","article-title":"Structure-function analysis of the OB and latch domains of chlorella virus DNA ligase","volume":"286","author":"Samai","year":"","journal-title":"J. Biol. Chem."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"28609","DOI":"10.1074\/jbc.M112.380428","article-title":"Kinetic analysis of DNA strand joining by Chlorella virus DNA ligase and the role of nucleotidyltransferase motif VI in ligase adenylylation","volume":"287","author":"Samai","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/s41586-023-06649-6","article-title":"A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes","volume":"623","author":"Sanderson","year":"2023","journal-title":"Nature"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"e0049421","DOI":"10.1128\/AAC.00494-21","article-title":"Characteristics of helicase-primase inhibitor amenamevir-resistant herpes simplex virus","volume":"65","author":"Sato","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"115322","DOI":"10.1016\/j.bcp.2022.115322","article-title":"Acyclovir resistance in herpes simplex viruses: prevalence and therapeutic alternatives","volume":"206","author":"Schalkwijk","year":"2022","journal-title":"Biochem. 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Chem."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"E3900","DOI":"10.1073\/pnas.1323705111","article-title":"One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities","volume":"111","author":"Subissi","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"e1007742","DOI":"10.1371\/journal.ppat.1007742","article-title":"DNA polymerase alpha is essential for intracellular amplification of hepatitis B virus covalently closed circular DNA","volume":"15","author":"Tang","year":"2019","journal-title":"PLoS Pathog."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1038\/s41467-017-01542-z","article-title":"The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding","volume":"8","author":"Tarbouriech","year":"2017","journal-title":"Nat. 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Virol."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"e49254","DOI":"10.1371\/journal.pone.0049254","article-title":"Cell penetrable humanized-VH\/V(H)H that inhibit RNA dependent RNA polymerase (NS5B) of HCV","volume":"7","author":"Thueng-in","year":"2012","journal-title":"PLoS One"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"104925","DOI":"10.1016\/j.antiviral.2020.104925","article-title":"Hepatitis B virus biology and life cycle","volume":"182","author":"Tsukuda","year":"2020","journal-title":"Antivir. Res."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"153","DOI":"10.2165\/00003495-199447010-00009","article-title":"Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy","volume":"47","author":"Wagstaff","year":"1994","journal-title":"Drugs"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41422-020-0282-0","article-title":"Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro","volume":"30","author":"Wang","year":"","journal-title":"Cell Res."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1038\/s41467-020-16234-4","article-title":"Stringent control of the RNA-dependent RNA polymerase translocation revealed by multiple intermediate structures","volume":"11","author":"Wang","year":"","journal-title":"Nat. Commun."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cell.2020.05.034","article-title":"Structural basis for RNA replication by the SARS-CoV-2 polymerase","volume":"182","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"e01888","DOI":"10.1128\/JVI.01888-18","article-title":"A nanobody targeting viral nonstructural protein 9 inhibits porcine reproductive and respiratory syndrome virus replication","volume":"93","author":"Wang","year":"2019","journal-title":"J. Virol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nature17180","article-title":"Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys","volume":"531","author":"Warren","year":"2016","journal-title":"Nature"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1517\/14728222.2013.827663","article-title":"The DNA helicase-primase complex as a target for herpes viral infection","volume":"17","author":"Weller","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3390\/v10010024","article-title":"Visualizing the nucleotide addition cycle of viral RNA-dependent RNA polymerase","volume":"10","author":"Wu","year":"2018","journal-title":"Viruses"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1146\/annurev-virology-093020-013659","article-title":"Liquid phase partitioning in virus replication: observations and opportunities","volume":"9","author":"Wu","year":"2022","journal-title":"Annu. Rev. Virol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"e2211425120","DOI":"10.1073\/pnas.2211425120","article-title":"Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases","volume":"120","author":"Wu","year":"","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"104872","DOI":"10.1016\/j.jbc.2023.104872","article-title":"Crystal structure of African swine fever virus pE301R reveals a ring-shaped trimeric DNA sliding clamp","volume":"299","author":"Wu","year":"","journal-title":"J. Biol. Chem."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41422-023-00796-1","article-title":"Cryo-EM structures of human monkeypox viral replication complexes with and without DNA duplex","volume":"33","author":"Xu","year":"2023","journal-title":"Cell Res."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1046\/j.1365-2443.1996.07007.x","article-title":"Clamp loading, unloading and intrinsic stability of the PCNA, beta and gp45 sliding clamps of human, E. 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Biol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1360\/SSV-2023-0107","article-title":"Manipulation of the cellular cytoskeleton-membrane network for virus replication (in Chinese)","volume":"54","author":"Zhang","year":"2024","journal-title":"Sci. Sin. Vitae"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"8811","DOI":"10.1093\/nar\/gkab666","article-title":"An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase","volume":"49","author":"Zhang","year":"","journal-title":"Nucleic Acids Res."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S1097-2765(00)80422-0","article-title":"The crystal structure of an unusual processivity factor, herpes simplex virus UL42, bound to the C terminus of its cognate polymerase","volume":"5","author":"Zuccola","year":"2000","journal-title":"Mol. 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