TY - JOUR
T1 - Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants
AU - Zarn, Katherine E.
AU - Jaramillo, Sierra A.
AU - Zapata, Anthony R.
AU - Stone, Nathan E.
AU - Jones, Ashley N.
AU - Nunnally, Haley E.
AU - Settles, Erik W.
AU - Ng, Ken
AU - Keim, Paul S.
AU - Knudsen, Steen
AU - Nuijten, Patricia M.
AU - Tijsma, Aloys S.L.
AU - French, Christopher T.
N1 - Publisher Copyright:
© 2022 Zarn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0272916
DO - 10.1371/journal.pone.0272916
M3 - Article
C2 - 36103462
AN - SCOPUS:85138448042
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 9 September
M1 - e0272916
ER -