Viral ‘molecular scissor’ is next COVID-19 drug target: Coronavirus uses enzymatic cutter for virus production and to disable essential immune proteins
SAN ANTONIO, Oct.18, 2020 /PRNewswire-PRWeb/ — American and Polish scientists, reporting Oct. 16 in the journal Science Advances, laid out a novel rationale for COVID-19 drug design – blocking a molecular “scissor” that the virus uses for virus production and to disable human proteins crucial to the immune response.
The researchers are from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and the Wroclaw University of Science and Technology. Information gleaned by the American team helped Polish chemists to develop two molecules that inhibit the cutter, an enzyme called SARS-CoV-2-PLpro.
SARS-CoV-2-PLpro promotes infection by sensing and processing both viral and human proteins, said senior author Shaun K. Olsen, PhD, associate professor of biochemistry and structural biology in the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio.
“This enzyme executes a double-whammy,” Dr. Olsen said. “It stimulates the release of proteins that are essential for the virus to replicate, and it also inhibits molecules called cytokines and chemokines that signal the immune system to attack the infection,” Dr. Olsen said.
SARS-CoV-2-PLpro cuts human proteins ubiquitin and ISG15, which help maintain protein integrity. “The enzyme acts like a molecular scissor,” Dr. Olsen said. “It cleaves ubiquitin and ISG15 away from other proteins, which reverses their normal effects.”
Dr. Olsen’s team, which recently moved to the Long School of Medicine at UT Health San Antonio from the Medical University of South Carolina, solved the three-dimensional structures of SARS-CoV-2-PLpro and the two inhibitor molecules, which are called VIR250 …