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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1546946
Efficacy of dispirotripiperazine PDSTP in a golden Syrian hamster model of SARS-CoV-2 infection/pneumonia
Provisionally accepted
Giuseppina Sanna 1,2*
Olga Riabova 3,4
Anna Egorova 3,4
Elena Kazakova 3,4 Alexander Lepioshkin 3,4 Natalia Monakhova 3,4 Alessandra Marongiu 2
Gianluigi Franci 5 Aldo Manzin 2
Vadim Makarov 3,4*- 1 University of Cagliari, Cagliari, Sardinia, Italy
- 2 Department of Biomedical Sciences, Faculty of Medicine and Surgery, University of Cagliari, Cagliari, Sardinia, Italy
- 3 Russian Academy of Sciences (RAS), Moscow, Moscow Oblast, Russia
- 4 Federal Center Research Fundamentals of Biotechnology (RAS), Moscow, Moscow Oblast, Russia
- 5 Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Campania, Italy
The increasing incidence of viral pandemics calls for new small molecule therapeutics that go beyond traditional approaches and targets.Dipirotripiperazine, 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 hostpathogen interactions. Here, 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.
Keywords: SARS-CoV-2, Dispirotripiperazine, in vitro, hamster model, Adhesion, efficacy
Received: 17 Dec 2024; Accepted: 10 Feb 2025.
Copyright: © 2025 Sanna, Riabova, Egorova, Kazakova, Lepioshkin, Monakhova, Marongiu, Franci, Manzin and Makarov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Giuseppina Sanna, University of Cagliari, Cagliari, 09124, Sardinia, Italy
Vadim Makarov, Federal Center Research Fundamentals of Biotechnology (RAS), Moscow, 119071, Moscow Oblast, Russia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.