4.6 Article

Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants

Journal

PLOS ONE
Volume 17, Issue 9, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0272916

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Funding

  1. Flinn Foundation [2304]
  2. Cowden Endowment for Microbiology (a private endowment through the Northern Arizona University Foundation)
  3. Arizona Board of Regents Technology and Research Initiative Fund

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A recent study found that the poly (ADP-ribose) polymerase (PARP) inhibitor stenoparib effectively inhibits various strains of SARS-CoV-2 in vitro, including the alpha variant, with the combination of remdesivir resulting in a synergistic effect.
We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Here we show that stenoparib effectively inhibits a SARS-CoV-2 wild type (BavPat1/2020) strain and four additional variant strains; alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) and gamma (P.1) in vitro, with 50% effective concentration (EC50) estimates of 4.1 mu M, 8.5 mu M, 24.1 mu M, 8.2 mu M and 13.6 mu M, respectively. A separate experiment focusing on a combination of 10 mu M stenoparib and 0.5 mu M remdesivir, an antiviral drug, resulted in over 80% inhibition of the alpha variant, which is substantially greater than the effect achieved with either drug alone, suggesting at least additive effects from combining the different mechanisms of activity of stenoparib and remdesivir.

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