Tecovirimat and mpox: A paradigm of the opportunities and limitations of antiviral drug repurposing
Emerging infectious diseases, such as mpox virus, continue to be a major challenge to global public health as they arise from zoonotic spillover, are maintained via sustained human transmission and viral evolution, and possess few to no virus-specific treatments. An important clinical pathway for rapid delivery of an antiviral to an emergent outbreak is via the repurposing of established drugs, for which safety and pharmacokinetic information already exist and have been thoroughly assessed. In this review, we assess tecovirimat as a case study of antiviral drug repurposing to demonstrate the potential and challenges of this approach based on available mechanistic studies, clinical trial results, long evolutionary history, and innovative future directions. Developed initially for smallpox under a biodefense program, tecovirimat blocks the highly conserved VP37 (F13L) envelope protein and was quickly adopted for mpox based on robust mechanistic justification, animal efficacy, and an established safety history. This reflects how past biodefense investment can be used to deploy therapies quickly against novel pathogens during emerging threats. The review critically analyzes disparities between promising observational studies and subsequent randomized clinical trial evidence. PALM007, STOMP, UNITY, and PLATINUM-UK failed to demonstrate any significant clinical advantage in the trials, and a comprehensive European Medicines Agency assessment determined that tecovirimat did not expedite lesion recovery, reduce pain, or result in improved virologic results compared to placebo. Thus, the European mpox indication for tecovirimat was removed in 2026. We also summarize the recent findings on the development of VP37-associated resistance mutations and briefly discuss how best practices, including genomic surveillance, antiviral stewardship, and rational combination therapy strategies, are needed to manage the ongoing threat of resistance and improve future outbreak therapeutics.
Sharma P. Tecovirimat and mpox: A paradigm of the opportunities and limitations of antiviral drug repurposing. J Appl Biol Biotech 2026. Article in Press. http://doi.org/10.7324/jabb.2026.327840
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