Design and Synthesis of Novel Compounds for Spike Protein Inhibition

Abstract

The Coronavirus disease 2019 (COVID-19) first emerged in December 2019 is caused by the virus SARS-CoV-2 which genetically resembles SARS-CoV, causative agent of Severe Acute Respiratory Syndrome (SARS) epidemic in 2002. The entry of the virus in the host cell is facilitated by Spike Glycoprotein (S protein) which protrudes from the viral envelope. The Receptor binding domain (RBD) of the S protein interacts with the ACE2 receptor present on the host cell followed by cleavage of S protein at the cleavage site and enters the host cell. Spike glycoprotein is one of the potential targets to inhibit the SARS-CoV-2 infection as it is exposed on the viral surface. Till now, no proper therapeutic agents are available to treat SARS-CoV-2 infection. In this study, a 5-point Pharmacophore hypothesis was generated by using phase by the residual selection of spike protein (PDB ID 6M0J). The created pharmacophore hypothesis was validated and database screening of ChEMBL library containing active compounds was done. From the screening results and literature review a new set of compounds were designed. These compounds were screened by molecular docking method and the compounds with good docking score were synthesized.