Novel Potential Candidate for the Treatment of Coronavirus

COVID-19 was identified as a new, potentially fatal, respiratory infection caused by SARS-CoV-2 in December 2019. Unlike the previous coronavirus outbreaks, the COVID-19 pandemic spread across the globe and as of September 2020, 29 million people are infected. The drug candidate “PF-00835231” discussed in the current study acts on the SARS-CoV-2 main protease i.e. 3C-like protease. This action is required for viral replication since it causes the large viral polyprotein p1a/p1ab to be cleaved at 10 or more junctions.

As a result, several non-structural proteins that play a crucial part in viral replication and transcriptions are produced like RdRp, the helicase, and the 3CLpro. The researchers found that both PF-00835231 and its phosphate prodrug have antiviral activity against a broad spectrum of coronaviruses. This allows the drug to inhibit several CoV 3CLpro enzymes in vitro, from alpha-, beta- and gamma-CoVs.

Cellular activity

After examining the capability of PF-00835231 to exert antiviral activity against SARS-CoV-2 in cell culture, it was found that there was a dose-dependent but steep suppression of viral activity with this molecule. When the activity was repeated using cell lines similar to the human lung cells, they obtained similarly promising results. Hence it was clear that this drug candidate has in vitro antiviral activity even as a single agent.

Combination of PF-00835231 with Remdesivir

Evaluation of the combined activity of these drugs led to the conclusion that they showed a mix of synergistic and additive effects. This could be because different convalescent sera were employed for the detection process. It was also found that the novel drug candidate is not easily metabolized reducing the chances of drug-drug interactions when used alongside other drugs. As a result, the data interpreted that PF-00835231 could be used as an intravenous infusion for optimal efficacy. If this drug performs like remdesivir, it may take 10 days of administration to improve patient outcomes.

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