SARS-COV-2 is a single stranded RNA virus with high mutation rate. The Delta variant is the predominant SARS-COV-2 variant, accounting for more than 99% of Covid-19 cases and leading to an overwhelming increase in some states. As COVID-19 gene mutation may reduce vaccine potency, the research and development of broad-spectrum anti coronavirus new drug becomes very important.

"Potential" player - PF-07321332

Currently there are two main approaches to discover drugs to treat COVID-19: small molecular compounds, and biological macromolecules dominated by antibodies. Small molecule compounds can inhibit the adsorption, invasion, replication, assembly, and release of virus. Pfizer's PF-07321332, a 3CL protease (3CLpro) inhibitor, is an oral antiviral therapeutic, targeting the SARS-CoV-2 coronavirus to prevent COVID-19 (Fig. 1). 3CL protease is the major protease shared by various coronaviruses. Therefore, the potential advantage of PF-07321332 is its possible role in all COVID-19 variants.

Fig 1: PF-07321332 structure

Beside PF-07321332, there are several other inhibitors of 3CL protease, including Zanamivir, Saquinavir mesylate, Rhoifolin, Dieckol, Pectolinarin and Amentoflavone, etc. In addition, Molnupiravir has been authorized by FDA for its emergency use, and S217622 is in clinical trial.

Fig2: 3CL protease is one of the important targets for the development of anti-COVID-19 drugs.