Researchers design new molecules to inhibit viral replication in SARS-CoV-2

Novel molecules have been designed as potential inhibitors of the viral main protease

Novel molecules designed as potential inhibitors of the viral Main protease

Summary

As part of the National Virtual Biotechnology Laboratory, a U.S. Department of Energy consortium dedicated to COVID-19, researchers are designing novel molecules as potential inhibitors of the SARS-CoV-2 viral main protease, an enzyme that plays an important role in viral replication and thus infection. After the virus infects a human cell, the infected cell reads the viral RNA – the instructions that define the viral genome – and makes a single protein chain that contains 16 viral proteins, all connected together. The viral main protease cuts apart that single protein chain into 16 mature, individual proteins, and is therefore necessary for the virus to replicate and infect other cells. The research team is hunting for small molecules that block the protease from making those cuts as a potential future therapeutic for COVID-19. Made for the first time by synthetic chemists, the new inhibitors contain unique electrophiles, chemical groups that connect directly to an important sulfur atom in the viral main protease by accepting electrons. Once researchers experimentally test and validate the inhibitors in a biochemical assay for the SARS-CoV-2 main protease, they will use computational algorithms to further design modifications to improve electron affinity and other properties of the original designer molecule.