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

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.

 

Comments:

That's interesting! It seems that your preliminary assessment has found promising results regarding the activity of the PARP inhibitor stenoparib (2X-121) against various strains of SARS-CoV-2, including the wild type and four different variants. The inhibitory effects were measured using the 50% effective concentration (EC50) estimates.

The EC50 estimates for stenoparib against the different strains are as follows:
- SARS-CoV-2 wild type (BavPat1/2020): 4.1 μM
- Alpha variant (B.1.1.7): 8.5 μM
- Beta variant (B.1.351): 24.1 μM
- Delta variant (B.1.617.2): 8.2 μM
- Gamma variant (P.1): 13.6 μM

These results indicate that stenoparib effectively inhibits viral replication for all tested strains, with varying potency.

Additionally, you conducted a separate experiment combining stenoparib (10 μM) with remdesivir (0.5 μM), an antiviral drug. The combination showed over 80% inhibition of the alpha variant, which is significantly higher than the individual effects of either drug alone. This suggests that there may be additive effects when combining the different mechanisms of action of stenoparib and remdesivir.

These findings are encouraging and imply that stenoparib has potential as an effective treatment option against SARS-CoV-2 and its variants. However, further research and clinical studies would be needed to validate these results and determine the safety and efficacy of stenoparib in treating COVID-19.

Related Products

Cat.No. Product Name Information
S8419 Stenoparib (E7449) Stenoparib (E7449, 2X-121, MGI25036) is an orally bioavailable, brain penetrable, small molecule dual inhibitor of PARP1/2 and also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1/2), important regulators of canonical Wnt/β-catenin signaling. It has IC50 values of 1.0 and 1.2 nM for PARP1 and 2, respectively.

Related Targets

PARP