Coronavirus, a highly aggressive pathogen!
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causative agent of COVID-19, the ongoing pandemic that has claimed the lives of over 5.4 million people worldwide since it first appeared in December 2019. SARS-CoV-2 is a Betacoronavirus, one of four genera of Coronaviruses belonging to the family, Coronaviridae. The other three genera are the Alphacoronaviruses, Gammacoronaviruses and Deltacoronaviruses. The Gamma and Delta Coronaviruses do not infect humans, while the Alphacoronaviruses are responsible for approximately 30% of the annual common cold cases.
The Betacoronaviruses are comprised of three highly virulent strains, including (i) SARS-CoV, which appeared in 2002 with an associated mortality rate of 10 to 15 percent, (ii) MERS-CoV, which came on the seen in 2015, wielding a case-fatality rate of 34 to 37 percent, and (iii) SARS-CoV-2, the causative agent of the current pandemic (COVID-19) with a mortality rate of 2 to 3 percent.
In addition to the main protease (Mpro), which is shared among all coronaviruses, the Betacoronaviruses have a second virus-encoded protease called papain-like protease (PLpro). These two proteases are responsible for cleaving the initial expression products of the viral genome (polyproteins 1a and 1ab) at 15 different sites to produce 16 other mature virus proteins essential for viral replication. While Mpro cleaves the viral polyproteins 1a and 1ab at 12 different locations, PLpro cleaves polyprotein 1a at only 3 sites. PLpro is also involved in cleaving specific host proteins (various ubiquitinated proteins and ISG15), resulting in suppressing the host’s immune response. It is believed that PLpro is responsible for the enhanced pathogenicity of the Betacoronaviruses. Our COVID-19 Treatment is an inhibitor of PLpro.
Our COVID-19 Treatment
- On May 22, 2020, we filed a patent application in the United States for a new treatment for Coronavirus infection. Our patent application covers composition subject matter pertaining to small molecules to inhibit the Coronavirus proteases.
- In August 2020, we completed the synthesis of four different potential inhibitors of Coronavirus protease. These compounds are based on the technology described in our patent application filed on May 22, 2020.
- In September 2020, we completed the screening of our four compounds and subsequently identified a lead Anti-Coronavirus drug candidate, SBFM-PL4.
- We recently expanded our research efforts into finding additional PLpro inhibitors by entering into a collaboration agreement with the University of Arizona. The collaboration is focused on determining in vivo safety, pharmacokinetics, dose selection, and mice efficacy studies of three University of Arizona owned PLpro inhibitors. The Company holds the first option to negotiate for a commercial, royalty-bearing license for all intellectual property developed by University of Arizona under the collaboration.