Efficacy of dispirotripiperazine PDSTP in a golden Syrian hamster model of SARS-CoV-2 infection.

The increasing incidence of viral pandemics calls for new small-molecule therapeutics beyond traditional approaches and targets. Dispirotripiperazine, composed of two positively charged nitrogen atoms, represents an unusual scaffold in drug discovery campaigns, and molecules based on it are known to prevent virus infection by disrupting early host-pathogen interactions. In this study, the adhesion-blocking dispirotripiperazine core compound PDSTP was evaluated against SARS-CoV-2 in vitro and in vivo. We demonstrated that the molecule was acceptably active against two clinical isolates affecting the early stages of the SARS-CoV-2 cycle. In a hamster model of SARS-CoV-2 pneumonia, PDSTP treatment resulted in reduced viral loads in the lungs and turbinates and milder lung tissue lesions. Overall, these data support PDSTP as a preclinical candidate for the treatment of COVID-19.