Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in 2019, and its high pathogenicity, infectivity, and transmissibility have led to a global pandemic. Although several vaccines have been approved in different countries, most of the global population currently remains unvaccinated because of disparities in vaccine distribution and limited manufacturing capabilities (1). Owing to a lack of treatment options (particularly in low- and middle-income countries), the slow progression of vaccination, and the emergence of SARS-CoV-2 variants that elicit reduced responses to vaccines, there is an urgent need to identify therapeutics to reduce COVID-19 morbidity and mortality. On page 926 of this issue, White et al. (2) demonstrate that the small-molecule drug, plitidepsin, which is approved to treat relapsed and refractory multiple myeloma, possesses antiviral activity against SARS-CoV-2 and may be a promising drug candidate for treating COVID-19.