A5001826062- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- vaccines and immunoinformatics approaches
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
Zhejiang University
2022-2024
Westlake University
2021-2023
Xijing University
2021
Drug resistance poses a significant challenge in the development of effective therapies against SARS-CoV-2. Here, we identified two double mutations, M49K/M165V and M49K/S301P, 3C-like protease (3CLpro) that confer to novel non-covalent inhibitor, WU-04, which is currently phase III clinical trials (NCT06197217). Crystallographic analysis indicates M49K mutation destabilizes WU-04-binding pocket, impacting binding WU-04 more significantly than 3CLpro substrates. The M165V directly interferes...
Abstract The SARS-CoV-2 virus is the causal agent of ongoing pandemic coronavirus disease 2019 (COVID-19). There an urgent need for potent, specific antiviral compounds against SARS-CoV-2. 3C-like protease (3CLpro) essential enzyme replication and other coronaviruses, thus a target drug discovery. Nearly all inhibitors 3CLpro reported so far are covalent inhibitors. Here, we report development specific, non-covalent 3CLpro. most potent one, WU-04, effectively blocks replications in human...
ABSTRACT Drug resistance poses a significant challenge in the development of effective therapies against SARS-CoV-2. Here, we identified two double mutations, M49K/M165V and M49K/S301P, 3C-like protease (3CLpro) that confer to novel non-covalent inhibitor, WU-04. Crystallographic analysis indicates M49K mutation destabilizes WU-04 binding pocket, impacting more significantly than 3CLpro substrates. The M165V directly interferes with binding. S301P mutation, which is far from indirectly...
Abstract The 3C-like protease (3CLpro) of SARS-CoV-2 is an attractive drug target for developing antivirals against SARS-CoV-2. A few small molecule inhibitors 3CLpro are in clinical trials COVID-19 treatments and more being developed. One limiting factor development that the cellular activities such have to be evaluated a Biosafety Level 3 (BSL-3) or BSL-4 laboratory. Here, we design genetically encoded biosensors can used BSL-2 laboratories set up cell-based assays inhibitor discovery....