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<p>Over the past five years, amid the escalating threat of viral outbreaks, drug repurposing has emerged as a pivotal strategy for rapidly deploying existing pharmacological agents against newly emerging infectious diseases. This review provides a comprehensive analysis of drug repurposing efforts targeting major viral infections between 2020 and 2025, with a particular focus on clinical trials and intervention strategies. The background and growing significance of drug repurposing are discussed in the context of the urgent global demand for accelerated antiviral development. Key viral infections, including SARS-CoV-2, monkey pox virus, H1N1 influenza, dengue virus, Zika virus, and hepatitis B and C, are examined in detail, with an emphasis on therapeutic interventions and clinical trial outcomes. Tabulated data summarize the efficacy, target mechanisms, and trial phases of key repurposed drugs. Additionally, the integration of emerging technologies, particularly artificial intelligence and machine learning, has enhanced the identification of novel drug-virus interactions, thereby increasing the precision of repurposing strategies. The paradigm shift toward host-targeted therapies further offers an alternative approach by disrupting host factors essential for viral replication. Despite significant progress, clinical challenges such as drug resistance, dosing optimization, and safety concerns persist. Overall, this review underscores the evolving role of repurposed drugs as a strategic asset in combating current and future viral pandemics through an integrated, evidence-based framework. Unlike many prior reviews that focus on single pathogens or early in silico candidate lists, we (i) benchmarked computational predictions against Phase II–IV clinical outcomes and real-world evidence, (ii) compared host-directed versus virus-directed repurposing strategies across multiple viral families, and (iii) integrated organ-specific toxicity constraints to explain translational attrition and guide future trial design.</p> Graphical abstract <p></p>

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Drug repurposing against viral infections (2020–2025): clinical trials, computational strategies, and therapeutic interventions

  • 期刊论文

  • 发表日期：

    2026年3月25日

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  • Sumel Ashique,
  • Joy Das,
  • Utpal Bhui,
  • Anas Islam,
  • Tahreen Taj,
  • Md Yousuf Ansari,
  • Jyoti Maithani Kalra,
  • Md Sadique Hussain

摘要

Over the past five years, amid the escalating threat of viral outbreaks, drug repurposing has emerged as a pivotal strategy for rapidly deploying existing pharmacological agents against newly emerging infectious diseases. This review provides a comprehensive analysis of drug repurposing efforts targeting major viral infections between 2020 and 2025, with a particular focus on clinical trials and intervention strategies. The background and growing significance of drug repurposing are discussed in the context of the urgent global demand for accelerated antiviral development. Key viral infections, including SARS-CoV-2, monkey pox virus, H1N1 influenza, dengue virus, Zika virus, and hepatitis B and C, are examined in detail, with an emphasis on therapeutic interventions and clinical trial outcomes. Tabulated data summarize the efficacy, target mechanisms, and trial phases of key repurposed drugs. Additionally, the integration of emerging technologies, particularly artificial intelligence and machine learning, has enhanced the identification of novel drug-virus interactions, thereby increasing the precision of repurposing strategies. The paradigm shift toward host-targeted therapies further offers an alternative approach by disrupting host factors essential for viral replication. Despite significant progress, clinical challenges such as drug resistance, dosing optimization, and safety concerns persist. Overall, this review underscores the evolving role of repurposed drugs as a strategic asset in combating current and future viral pandemics through an integrated, evidence-based framework. Unlike many prior reviews that focus on single pathogens or early in silico candidate lists, we (i) benchmarked computational predictions against Phase II–IV clinical outcomes and real-world evidence, (ii) compared host-directed versus virus-directed repurposing strategies across multiple viral families, and (iii) integrated organ-specific toxicity constraints to explain translational attrition and guide future trial design.

Graphical abstract