It has been four years since the emergence of the COVID-19 pandemic, and the ongoing threat it poses to human health and life underscores the continued need for the development of antiviral medications as a means of mitigating future viral outbreaks. In this study, we present a novel class of antiviral compounds, naphthoquinone-fused enediyne sugar polysulfates, which have demonstrated efficacy against coronaviruses by targeting the conserved receptor binding domain on spike proteins. These compounds induce irreversible damage to the viral proteins that are essential for binding to host cells, resulting in inhibition of viral infection at nanomolar concentrations with minimal cytotoxic effects. Notably, the selectivity index of these compounds exceeds 50,000, suggesting significant potential for further development in antiviral therapeutics against coronavirus.

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