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PDSTP Is the First Drug in Class to Treat Coronavirus Infection.

V A Makarov1, V O Popov1

  • 1Federal Research Center, Fundamentals of Biotechnology, Russian Academy of Sciences, Moscow, Russia.

Herald of the Russian Academy of Sciences
|September 12, 2022
PubMed
Summary

A novel molecule, PDSTP, effectively blocks SARS-CoV-2 from infecting host cells by targeting the virus-cell electrostatic interaction. This antiviral candidate shows low toxicity and high efficacy in preclinical studies.

Keywords:
PDSTPSARS-CoV-2coronavirusdrug developmentheparan sulfate proteoglycan

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Area of Science:

  • Biochemistry
  • Virology
  • Drug Discovery

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) utilizes heparan sulfate proteoglycans (HSPGs) on host cell surfaces for initial attachment.
  • This interaction is a critical first step in the viral infection process.

Purpose of the Study:

  • To develop and characterize a novel small molecule, PDSTP, designed to inhibit SARS-CoV-2 cell entry.
  • To evaluate the efficacy and safety profile of PDSTP as a potential antiviral therapeutic.

Main Methods:

  • Design of the PDSTP molecule based on electrostatic interactions with HSPGs.
  • In vitro and in vivo experiments to assess PDSTP's ability to block viral binding and prevent infection.
  • Toxicology and safety profiling of the PDSTP molecule.

Main Results:

  • The PDSTP molecule was successfully synthesized and demonstrated the ability to electrostatically interact with cell surface HSPGs.
  • PDSTP effectively prevented the binding of SARS-CoV-2 to host cells, thereby inhibiting viral entry.
  • Animal studies showed good efficacy of PDSTP in preventing infection, coupled with a very low toxicity and high safety profile.

Conclusions:

  • The novel PDSTP molecule presents a promising therapeutic strategy for preventing SARS-CoV-2 infection by disrupting the initial viral attachment mechanism.
  • PDSTP's unique mechanism of action, low toxicity, and high safety profile warrant further clinical investigation as a potential antiviral agent.