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 - Funding Information:
This research was supported by a grant from The Flinn Foundation awarded to PSK (grant # 2304; https://flinn.org/), the Cowden Endowment for Microbiology (a private endowment through the Northern Arizona University Foundation), and an Arizona Board of Regents Technology and Research Initiative Fund award to PSK and CTF (https://www.azleg.gov/ars/15/01648.htm). Core experiments were supported by service fees paid by Allarity Therapeutics. SK received funding in the form of salary from the commercial organization Allarity Therapeutics. PMN and ASLT received funding in the form of salary from the commercial organization Viroclinics-DDL. The funders had no additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
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 -