A5104315804- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Peptidase Inhibition and Analysis
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Click Chemistry and Applications
- Bacterial Identification and Susceptibility Testing
- Oral microbiology and periodontitis research
- Nanocomposite Films for Food Packaging
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Food Chemistry and Fat Analysis
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Resistance in Staphylococcus
- Synthesis and Biological Evaluation
- Endodontics and Root Canal Treatments
- Agriculture and Agroindustry Studies
- thermodynamics and calorimetric analyses
- Ubiquitin and proteasome pathways
- Wireless Sensor Networks and IoT
- Biochemical and Molecular Research
- Hepatitis C virus research
Gansu Agricultural University
2024
Texas A&M University
2020-2024
Tianjin University
2024
Qingdao University
2022
Qingdao Municipal Hospital
2022
Dalian Medical University
2022
Jinan University
2021
Nankai University
2016-2021
State Key Laboratory of Medicinal Chemical Biology
2016-2019
We have witnessed three coronavirus (CoV) outbreaks in the past two decades, including COVID-19 pandemic caused by SARS-CoV-2. Main protease (MPro), a highly conserved among various CoVs, is essential for viral replication and pathogenesis, making it prime target antiviral drug development. Here, we leverage proteolysis targeting chimera (PROTAC) technology to develop new class of small-molecule antivirals that induce degradation SARS-CoV-2 MPro. Among them, MPD2 was demonstrated effectively...
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro ) to digest two of translated long polypeptides form a number mature proteins that are essential for viral replication and pathogenesis. Inhibition this vital proteolytic process is effective in preventing the virus from replicating infected cells therefore provides potential treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 (SC1MPro ), we have designed synthesized series SC2MPro inhibitors...
Abstract A number of inhibitors have been developed for the SARS‐CoV‐2 main protease (M Pro ) as potential COVID‐19 medications but little is known about their selectivity. Using enzymatic assays, we characterized inhibition TMPRSS2, furin, and cathepsins B/K/L by more than a dozen previously M including MPI1‐9, GC376, 11a, 10–1, 10–2, 10–3. GC376 11a all contain an aldehyde formation reversible covalent hemiacetal adduct with active site cysteine 10–2 10–3 labile ester to exchange...
As an essential enzyme of SARS-CoV-2, main protease (MPro) triggers acute toxicity to its human cell host, effect that can be alleviated by MPro inhibitor. Using this alleviation, we developed effective method allows a bulk analysis the cellular potency inhibitors. This novel assay is advantageous over antiviral in providing precise inhibition information assess We used analyze 30 known Contrary their strong effects and up 10 μM, 11a, calpain inhibitor II, XII, ebselen, bepridil,...
SARS-CoV-2, the COVID-19 pathogen, relies on its main protease (M
Targeted covalent inhibitors (TCIs) have attracted growing attention from the pharmaceutical industry in recent decades because they potential advantages terms of efficacy, selectivity, and safety. TCIs recently evolved into a new version with reversibility that can be systematically modulated. This feature may diminish risk haptenization help optimize drug–target residence time as needed. The enteroviral 3C protease (3Cpro) is valuable therapeutic target, but development 3Cpro far...
A recently reported potent inhibitor of enterovirus 71 3C protease, ( R)-1, was found to have stability and potential toxicity issues due the presence a cyanohydrin moiety. Modifying labile moiety, by serendipity, led discovery 4-iminooxazolidin-2-one-based inhibitors 4e 4g with inhibitory activity significantly improved stability. In vivo pharmacokinetic studies also demonstrated high plasma exposure moderate half-life. These compounds shown becoming anti-EV71 drug candidates.
The main protease (MPro) of SARS-CoV-2 is crucial for the virus's replication and pathogenicity. Its active site characterized by four distinct pockets (S1, S2, S4, S1-3') a solvent-exposed S3 accommodating protein substrate. During X-ray crystallographic analyses MPro bound with dipeptide inhibitors containing flexible N-terminal group, we often observed an unexpected binding mode. Contrary to anticipated engagement deeper S4 pocket, group frequently assumed twisted conformation,...
Microglia are the primary cellular source of type I interferons (I-IFNs) in brain upon neurotropic virus infection. Although I-IFN-based antiviral innate immune response is crucial for eliminating viruses, overproduction led to disorders. Therefore, relatively long-lasting I-IFNs must be precisely controlled, but regulatory mechanism microglia remains largely unknown. Long non-coding RNAs (lncRNAs) being recognized as factors numerous diseases, their roles undefined. Methods: The...
We have witnessed three coronavirus (CoV) outbreaks in the past two decades, including COVID-19 pandemic caused by SARS-CoV-2. Main protease (M
The fatal pathogen enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease (HFMD), which leads to serious neurological syndromes. While there are no effective clinical agents available for EV71 treatment thus far, 3C protease (3C
ABSTRACT As an essential enzyme of SARS-CoV-2, the pathogen COVID-19, main protease (M Pro ) triggers acute toxicity to its human cell host, effect that can be alleviated by M inhibitor with cellular potency. By coupling this alleviation expression -eGFP fusion protein in a host for straightforward characterization fluorescent flow cytometry, we developed effective method allows bulk analysis potency inhibitors. In comparison antiviral assay which inhibitors may target proteases or other...
ABSTRACT The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M Pro ) to digest two of translated polypeptides form a number mature proteins that are essential for viral replication and pathogenesis. Inhibition this vital proteolytic process is effective in preventing the virus from infected cells therefore provides potential treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 (SC1M ), we have designed synthesized series SC2M inhibitors contain β-(...
Boceprevir is an HCV NSP3 inhibitor that has been explored as a repurposed drug for COVID-19. It inhibits the SARS-CoV-2 main protease (M Pro ) and contains α-ketoamide warhead, P1 β-cyclobutylalanyl moiety, P2 dimethylcyclopropylproline, P3 tert -butyl-glycine, P4 N -terminal -butylcarbamide. By introducing modifications at all four positions, we synthesized 20 boceprevir-based M inhibitors including PF-07321332 characterized their inhibition potency in test tubes ( vitro human host cells...
Abstract Enterococcus faecalis ( E. ) is frequently encountered in asymptomatic, persistent endodontic infections; thus, its control and eradication via disinfectants are important. To explore a disinfectant formulation that effective yet with minimal side effects, here, we evaluated the susceptibility of to three intracanal disinfectants. We quantitatively assessed compared growth‐ or metabolism‐inhibiting effects minimum inhibitory concentration (MIC) based on metabolic activity (MIC‐MA),...