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- Title
Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants.
- Authors
Zarn, Katherine E.; Jaramillo, Sierra A.; Zapata, Anthony R.; Stone, Nathan E.; Jones, Ashley N.; Nunnally, Haley E.; Settles, Erik W.; Ng, Ken; Keim, Paul S.; Knudsen, Steen; Nuijten, Patricia M.; Tijsma, Aloys S. L.; French, Christopher T.
- Abstract
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 μM, 8.5 μM, 24.1 μM, 8.2 μM and 13.6 μM, respectively. A separate experiment focusing on a combination of 10 μM stenoparib and 0.5 μM 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.
- Subjects
POLY ADP ribose; SARS-CoV-2; SARS-CoV-2 Delta variant; ANTIVIRAL agents; REMDESIVIR; VIRAL replication; POLYMERASES
- Publication
PLoS ONE, 2022, Vol 17, Issue 9, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0272916