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Despite warnings, therapeutic tools that could be rapidly and sustainably scaled at a global level when SARS-CoV-2 emerged were lacking. Small-molecule antivirals can play a crucial role in both individual patient care and broader public health strategies for controlling and mitigating the impact of viral diseases. Despite their utility, the lack of R&amp;D investment in this class of intervention has prevented the world from reaping the benefits they can deliver. The INTREPID Alliance 2025 publication of the Antiviral Clinical and Preclinical Development Landscape\u20144th Edition, revealed significant gaps in the development pipeline. No antivirals are in clinical development for 4 of the 13 viral families designated by the World Health Organization as viral families of pandemic and endemic concern.<\/jats:p>","DOI":"10.1093\/cid\/ciaf476","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T11:35:24Z","timestamp":1756467324000},"page":"e49-e55","source":"Crossref","is-referenced-by-count":9,"title":["The Indispensable Value of Small-Molecule Antivirals in Epidemic and Pandemic Preparedness"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-4039","authenticated-orcid":false,"given":"Ruxandra","family":"Draghia-Akli","sequence":"first","affiliation":[{"name":"Research and Development, Novavax, Inc. , Gaithersburg, Maryland ,","place":["USA"]},{"name":"INTREPID Alliance , Cambridge, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-0991","authenticated-orcid":false,"given":"Nina M","family":"Hill","sequence":"additional","affiliation":[{"name":"INTREPID Alliance , Cambridge, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Altevogt","sequence":"additional","affiliation":[{"name":"KKCM Consulting Inc. , Silver Springs, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4757-5122","authenticated-orcid":false,"given":"Kenneth","family":"Bradley","sequence":"additional","affiliation":[{"name":"INTREPID Alliance , Cambridge, Massachusetts ,","place":["USA"]},{"name":"Infectious Disease Discovery, F. 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