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

Stenoparib 是一种细胞聚(ADP-核糖)聚合酶 (PARP) 抑制剂,可阻断 SARS-CoV-2 变体的体外复制

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作者: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 S L Tijsma, Christopher T French

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.

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