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Despite its limited host range and lack of zoonotic potential, ASF has severe socio-economic and environmental consequences. Current control strategies primarily rely on early detection and culling of infected animals, but these measures are insufficient given the rapid spread of the disease. Developing effective therapeutics against ASFV is crucial to prevent further spread and mitigate economic losses. Although vaccination remains critical, recent vaccine approvals in Vietnam have raised safety and efficacy concerns. Moreover, as challenges persist in vaccine development and deployment, particularly in complex field conditions, antiviral agents have emerged as a critical complementary approach. These agents have the potential to mitigate side effects and control viral spread when vaccines alone are insufficient or when animals face simultaneous exposure to vaccine strains and wild-type viruses. However, advancing them from proof-of-concept to widespread practical application entails a significant interdisciplinary effort, given the logistical and economic constraints of in vivo testing. In this review, we examine emerging antiviral approaches and highlight key ASFV replication mechanisms and therapeutic targets to guide rational drug design amidst an evolving viral landscape.<\/jats:p>","DOI":"10.1093\/femsre\/fuaf044","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T11:56:06Z","timestamp":1757073366000},"source":"Crossref","is-referenced-by-count":17,"title":["Exploring antiviral strategies to combat African swine fever"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-777X","authenticated-orcid":false,"given":"Ana Catarina","family":"Urbano","sequence":"first","affiliation":[{"name":"CIISA - Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon , Avenida da Universidade T\u00e9cnica, Lisbon, 1300-477 ,","place":["Portugal"]},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS) , 1300-477, Lisbon ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Melo","sequence":"additional","affiliation":[{"name":"CIISA - Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon , Avenida da Universidade T\u00e9cnica, Lisbon, 1300-477 ,","place":["Portugal"]},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS) , 1300-477, Lisbon ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Ferreira","sequence":"additional","affiliation":[{"name":"CIISA - Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon , Avenida da Universidade T\u00e9cnica, Lisbon, 1300-477 ,","place":["Portugal"]},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS) , 1300-477, Lisbon ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"2025091915565190800_bib2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/0168-1702(90)90071-I","article-title":"Interaction of African swine fever virus with macrophages","volume":"17","author":"Alcam\u00ed","year":"1990","journal-title":"Virus Res"},{"key":"2025091915565190800_bib1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/0042-6822(89)90511-4","article-title":"The entry of African swine fever virus into Vero cells","volume":"171","author":"Alcam\u00ed","year":"1989","journal-title":"Virology"},{"key":"2025091915565190800_bib3","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/0042-6822(91)90912-U","article-title":"Fc receptors do not mediate African swine fever virus replication in macrophages","volume":"181","author":"Alcam\u00ed","year":"1991","journal-title":"Virology"},{"key":"2025091915565190800_bib4","doi-asserted-by":"publisher","first-page":"5571","DOI":"10.1128\/JVI.77.10.5571-5577.2003","article-title":"African swine fever virus proteinase is essential for core maturation and infectivity","volume":"77","author":"Alejo","year":"2003","journal-title":"J Virol"},{"key":"2025091915565190800_bib5","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01293-18","article-title":"A proteomic atlas of the African swine fever virus particle","volume":"92","author":"Alejo","year":"2018","journal-title":"J Virol"},{"key":"2025091915565190800_bib6","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1002\/pmic.200300742","article-title":"Identification of cellular proteins modified in response to African swine fever virus infection by proteomics","volume":"4","author":"Alfonso","year":"2004","journal-title":"Proteomics"},{"key":"2025091915565190800_bib7","doi-asserted-by":"publisher","first-page":"707819","DOI":"10.3389\/fvets.2021.707819","article-title":"Prevention and control of African swine fever in the smallholder pig value chain in Northern Uganda: thematic analysis of stakeholders\u2019 Perceptions","volume":"8","author":"Aliro","year":"2022","journal-title":"Front Vet Sci"},{"key":"2025091915565190800_bib8","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1099\/jgv.0.001049","article-title":"ICTV Report Consortium. 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