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Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants
Katherine E Zarn; Sierra A Jaramillo; Anthony R Zapata; Nathan E Stone; Ashley N Jones; Haley E Nunnally; Erik W Settles; Ken Ng; Paul S Keim; Steen Knudsen; Patricia M Nuijten; Aloys SL Tijsma; Christopher T French.
Affiliation
  • Katherine E Zarn; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Sierra A Jaramillo; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Anthony R Zapata; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Nathan E Stone; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Ashley N Jones; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Haley E Nunnally; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Erik W Settles; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Ken Ng; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Paul S Keim; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
  • Steen Knudsen; Allarity Therapeutics, DK-2970 Horsholm, Denmark
  • Patricia M Nuijten; Viroclinics-DDL, Rotterdam, The Netherlands
  • Aloys SL Tijsma; Viroclinics-DDL, Rotterdam, The Netherlands
  • Christopher T French; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011-4073
Preprint in English | bioRxiv | ID: ppbiorxiv-467186
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 wt (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 M, 8.5 M, 24.1 M, 8.2 M and 13.6 M, respectively. A separate experiment focusing on a combination of 10 M stenoparib and 0.5 M remdesivir, an antiviral drug, resulted in over 80% inhibition of the alpha (B.1.1.7) 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.
License
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
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