Nucleoside analogues for the treatment of coronavirus infections

Highlights • Coronaviruses (CoV) represent current and future risk for pandemic zoonotic infections. • Nucleoside analogues are highly active across multiple virus families. • CoVs encode a proofreading exoribonuclease that opposes inhibition by many nucleoside analogues. • Remdesivir is an adenosine analogue that acts against a broad spectrum of CoVs. • Other nucleoside analogues show promise against CoVs.
Recent outbreaks of SARS-Coronavirus and MERS-Coronavirus (CoV) have heightened awareness about the lack of vaccines or antiviral compounds approved for prevention or treatment of human or potential zoonotic CoVs. Anti-CoV drug development has long been challenged by the activity of a 3′ to 5′ proofreading exoribonuclease unique to CoVs. Recently, a promising nucleoside analogue with broad-spectrum activity against CoVs has been identified. This review will discuss progress made in the development of antiviral nucleoside and nucleotide analogues targeting viral RNA synthesis as effective therapeutics against CoV infections and propose promising strategies for combination therapy.