Development of Novel Therapeutics for the Treatment of COVID-19: Targeting the SARS-CoV-2 Protease, Spike RBD protein and RNAdependent RNA polymerase Enzyme.

The genome of SARS-CoV-2 translates non-structural proteins [SARS-CoV-2 Mpro (main protease), RNA-dependent RNA polymerase (RdRp)], structural proteins (spike glycoprotein), and other accessory proteins. The non-structural proteins play a key role during the virus's life cycle, and spike glycoprotein is necessary for the interactions of the virus with the host cell receptors during viral entry. These were recognized as promising targets for the development of broad-spectrum antiviral therapeutic agents. Thus, drugs targeting these proteins are usually capable of preventing the replication and proliferation of the virus and display broad-spectrum antiviral activity. In addition, dual drug targeting of these enzymes, represents a novel approach that can reduce the risk of mutation-mediated drug resistance in current and future emerging deadly strains. Thus, in collaboration with our colleagues at Harvard University and MIT, we have screened our compound libraries using in silico molecular modeling against SARS-CoV-2 drug targets and identified several lead compounds with unique chemical structures that bind and inhibit two key enzymes required for viral replication, namely the Proteases and RNA dependent RNA polymerase. Therefore, our research aims at translating these findings to develop novel molecules to combat COVID-19.