The PARP inhibitor stenoparib inhibits the pre- and post-invasion process of SARS-CoV-2 in vitro

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China in late December 2019, spread rapidly around the world, and developed into a catastrophic pandemic. To date, the COVID-19 pandemic has infected 54.3 million people worldwide and killed more than 1.31 million people.

In the absence of vaccine, COVID-19 can continue to cause significant morbidity and mortality

Coronavirus disease (COVID-19) affects the upper and lower respiratory tracts and causes flu-like symptoms in most infected individuals. Many people infected with SARS-CoV-2 experience mild symptoms, but some patients have severe symptoms, causing extensive lung damage. Treatment options for COVID-19 are limited, with mortality rates ranging from 0.5% to 5%.

Johns Hopkins COVID Resource Center As of November 15, 2020, it is estimated that there are more than 11 million COVID-19 infections and more than 246,000 deaths in the United States. Although SARS-CoV-2 prophylactic vaccines may eventually become available unless sufficient herd immunity is achieved, COVID-19 can cause significant morbidity and mortality over the next few years. There is sex.

In the absence of preventative vaccines, COVID-19 has been working with non-pharmaceutical public health interventions such as blockade, social isolation, quarantine, and the use of personal protective equipment. Clearly, prophylactic vaccines against SARS-CoV-2 and effective treatments for COVID-19 disease are urgently needed to combat this unprecedented pandemic.

Evaluation of in vitro activity of stenoparib against SARS-CoV-2

A team of researchers at Northern Arizona University evaluated a new PARP inhibitor, stenoparib. It has recently advanced to Stage II of clinical trials for the treatment of ovarian cancer.Their study, the first report on in vitro stenoparib activity in humans Coronavirus SARS-CoV-2 etc. are published on the preprint server bioRxiv*.

During the study, stenoparib showed a dose-dependent suppression of SARS-CoV-2 proliferation and diffusion in Vero E6 monkey kidney and Calu-3 human lung adenocarcinoma cells. Stenoparib also strongly inhibited the growth of seasonal HCoVNL63 human respiratory coronavirus.

Stenoparib blocks both virus invasion and post-invasion processes

Addition time experiments have shown that stenoparib inhibits both viral invasion and post-invasion events compared to the drug remdesivir, which inhibits viral replication after invasion of host cells. In addition, the combination of 10 µM stenoparib and 0.5 µM remdesivir suppressed coronavirus growth by 90.7%. This shows a strong synergistic effect on this combination of drugs. Interestingly, the 10 µM dose of stenoparib is well below half of its 25.5 µM maximum effective concentration (EC50).

“Overall, our observations imply multiple mechanisms of stenoparib, including viral invasion and inhibition of intracellular proliferation through modification of multiple viruses and host proteins.”

Based on these results, the authors conclude that stenoparib could be a valuable weapon in the fight against the COVID-19 pandemic, either as a stand-alone solution or in combination with drugs such as remdesivir. It was.

The wide range of effects of stenoparib may offer therapeutic benefits over current options

In the light of unprecedented threats to global public health and the economy, it is clear that there is an urgent need for new treatments in the fight against COVID-19. You can move toward this goal by diverting existing drugs that are approved for human use or are in the process of clinical trials.

Researchers have found that the safety and dosage of stenoparib in humans has already been established, and stenoparib, a PARP inhibitor currently undergoing stage II clinical trials for the treatment of ovarian cancer, may be such. I think there is sex. The results of this study show that stenoparib has strong in vitro antiviral activity against SARS-CoV-2 virus and other coronaviruses. This antiviral activity appears to be based on multiple mechanisms of action that inhibit both pre- and post-invasion viral replication events.

The authors state that this broad range of effects of stenoparib may offer therapeutic benefits over other currently available options with a narrower mechanism of action. In addition, their results clearly suggest that the combination of stenoparib and remdesivir may be a powerful therapeutic solution for coronavirus infection.

“Given their clear mechanism and high potency, the combination of remdesivir and stenoparib may have a synergistic effect on additional SARS family coronaviruses, including SARS-CoV-2.”

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical / health-related behaviors, and should not be treated as established information.