Broad-spectrum prodrugs with anti-SARS-CoV-2 activities: Strategies, benefits, and challenges.

In this era, broad-spectrum prodrugs with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activities are gaining considerable attention owing to their potential clinical benefits and role in combating the fast-spreading coronavirus disease 2019 (COVID-19) pandemic. The last 2 years have seen a surge of reports on various broad-spectrum prodrugs against SARS-CoV-2, and in in vitro studies, animal models, and clinical practice. Currently, only remdesivir (with many controversies and limitations) has been approved by the U.S. FDA for the treatment of SARS-CoV-2 infection, and additional potent anti-SARS-CoV-2 drugs are urgently required to enrich the defense arsenals. The world has ubiquitously grappled with the COVID-19 pandemic, and the availability of broad-spectrum prodrugs provides great hope for us to subdue this global threat. This article reviews promising treatment strategies, antiviral mechanisms, potential benefits, and daunting clinical challenges of anti-SARS-CoV-2 agents to provide some important guidance for future clinical treatment.