A Chemical Strategy for the Degradation of the Main Protease of SARS-CoV-2 in Cells
Xiaohong Sang, Juan Wang, Jiao Zhou, Yan Xu, Jing An, Arieh Warshel, Ziwei Huang
Abstract
SARS-CoV-2 is the virus that causes the global pandemic of COVID-19. The main protease (M pro ) of SARS-CoV-2 is essential for viral infection and is one of the major therapeutic targets for COVID-19. Here, we report the design, synthesis, and biological characterization of a novel heterobifunctional small molecule that could effectively induce the degradation of SARS-CoV-2 M pro and its drug-resistant mutants in HEK 293T cells, thus demonstrating a new alternative strategy for intervening with proteins important for this novel coronavirus.
Topics & Concepts
ChemistryProteaseHEK 293 cellsCoronavirusSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)Mutant2019-20 coronavirus outbreakVirusVirologyDrug discoveryDegradation (telecommunications)Small moleculeSevere acute respiratory syndrome coronavirusComputational biologyBiochemistryEnzymeBiologyGeneMedicineComputer sciencePathologyTelecommunicationsOutbreakInfectious disease (medical specialty)DiseaseSARS-CoV-2 and COVID-19 ResearchRNA Interference and Gene DeliveryProtein Degradation and Inhibitors