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

## TL;DR

This study shows that a new compound called PDSTP can reduce SARS-CoV-2 infection in hamsters, suggesting it may be a promising treatment for COVID-19.

## Contribution

The study introduces PDSTP, a dispirotripiperazine compound, as a novel preclinical candidate for treating SARS-CoV-2.

## Key findings

- PDSTP showed acceptable activity against two SARS-CoV-2 clinical isolates in early infection stages.
- PDSTP treatment reduced viral loads in hamster lungs and turbinates.
- PDSTP led to milder lung tissue lesions in infected hamsters.

## Abstract

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.