Drug Repurposing as a Broad-Spectrum Strategy Against Coronaviruses: Frontiers in Mechanisms and Clinical Translation

Coronaviruses (family Coronaviridae) are enveloped, positive-sense, single-stranded RNA viruses with broad host adaptability. They transmit across species among humans, livestock, companion animals, and wildlife, eliciting a disease spectrum ranging from mild respiratory and gastrointestinal symptoms to fatal multi-organ failure, thereby posing significant challenges to global health. In this context, drug repurposing has emerged as a practical strategy for rapidly identifying broad-spectrum antivirals against emerging and re-emerging coronaviruses. Using coronaviruses as a paradigm, this review systematically summarizes research advances and mechanistic insights into the repurposing of existing drugs against coronaviruses. Simultaneously, we dissect core challenges including species-specific pharmacokinetic disparities, insufficient inter-genera conservation of viral targets, and systemic barriers between human and veterinary drug regulatory frameworks and propose innovative solutions encompassing AI-driven cross-species drug prediction, next-generation cross-species infection models, and a “human-veterinary dual-track” collaborative research and development system. Collectively, this review highlights the promise of drug repurposing as a broad-spectrum antiviral strategy and provides a translational perspective for the development of cross-species anti-coronavirus therapeutics.