Drug repurposing and other strategies for rapid coronavirus antiviral development: lessons from the early stage of the COVID-19 pandemic

The recent and recurrent spillover of three highly pathogenic coronaviruses, SARS-CoV-1, MERS-CoV and SARS-CoV-2, into human populations has stressed the importance of pandemic preparedness. Here, we describe how, in the absence of antiviral therapeutic options against coronaviruses, early clinical investigations have focused on the prompt repurposing of approved antiviral therapies. We discuss how, despite international collaborative efforts, their outcomes so far have been disappointing as none of the early drugs tested demonstrated effective clinical efficacy. We also outline innovative strategies and tools developed to fast-track development of novel classes of antivirals. These capitalise on a deeper understanding of viral molecular pathogenesis and how coronaviruses hijack the host cellular machinery to maximise their replication and counteract host defences. Collectively, these approaches are crucial to identify and validate novel targets for therapeutic interventions and expand the repertoire of broad-spectrum antiviral agents, so that these can be promptly deployed for current and future pandemics.Copyright © ERS 2021.