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Recent studies have shown that LRP\u20101 is the receptor for a spectrum of viruses of great relevance to human and animal health. Rift Valley fever virus (RVFV), Oropouche virus (OROV), Severe fever with thrombocytopaenia syndrome virus (SFTSV), Dengue virus (DENV), Sicilian sandfly fever virus (SFSV), La Crosse virus (LACV), Jamestown Canyon virus (JCV), and Chandipura virus (CHPV) interact with LRP\u20101 for their infection in mammalian hosts cells. They are included in the arbovirus group, provoke acute disease with significant health implications and present a high risk of transmission from their endemic regions. Currently, none of these viruses have a specific antiviral or vaccine for the treatment of the disease, therefore the development of an antiviral blocking LRP\u20101 functions would have great scope and potential. In this review, we searched for the current evidence of the validation of LRP\u20101 as a cellular target for a wide range of RNA genome viruses, highlighting common features of these viruses and the regulation of LRP\u20101 mediated intracellular signalling in different cell types. In addition, the advantages of an antiviral using LRP\u20101 as molecular target are discussed, along with the risks and challenges involved in blocking its activity.<\/jats:p>","DOI":"10.1002\/rmv.70136","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:49:56Z","timestamp":1778755796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LRP\u20101 as Target of Broad\u2010Specific Antivirals: Benefits, Risks and Challenges"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9082-4146","authenticated-orcid":false,"given":"Daniela Isabel","family":"Maldonado\u2010Bauz\u00e1","sequence":"first","affiliation":[{"name":"Department of Systems Biology Biomedical Research. 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