A5039312658- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- Synthesis and biological activity
- Click Chemistry and Applications
- Cell death mechanisms and regulation
- Immune Response and Inflammation
- ATP Synthase and ATPases Research
- Toxin Mechanisms and Immunotoxins
- RNA and protein synthesis mechanisms
- Natural product bioactivities and synthesis
- Influenza Virus Research Studies
- Poxvirus research and outbreaks
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Synthesis and Characterization of Heterocyclic Compounds
- Herpesvirus Infections and Treatments
- Cancer therapeutics and mechanisms
ShanghaiTech University
2024-2025
Shanghai Institute of Materia Medica
2021-2024
Chinese Academy of Sciences
2021-2024
Nanjing University of Chinese Medicine
2021-2023
University of Chinese Academy of Sciences
2023
The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) and its variants accentuates the great demand for developing effective therapeutic agents. Here, we report development an orally bioavailable SARS-CoV-2 3C-like protease (3CL
The main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target in coronaviruses because its crucial involvement viral replication and transcription. Here, we report on the design, synthesis, structure-activity relationships novel small-molecule thioesters as Mpro inhibitors. Compounds 3w 3x exhibited excellent inhibition with kinac/Ki 58,700 M-1 s-1 (Ki = 0.0141 μM) 27,200 0.0332 μM), respectively. In Calu-3 Vero76 cells, compounds 3h, 3i, 3l, 3r, 3v, 3w, displayed antiviral activity...
3CLpro is an attractive target for the treatment of COVID-19. Using scaffold hopping strategy, we identified a potent inhibitor (3a) that contains thiocyanate moiety as novel warhead can form covalent bond with Cys145 protein. Tandem mass spectrometry (MS/MS) and X-ray crystallography confirmed mechanism formation between 3a protein in its catalytic pocket. Moreover, several analogues compound were designed synthesized. Among them, 3h shows best inhibition IC50 0.322 μM kinact/Ki value...
Abstract Sepsis, characterized with high risk of life‐threatening organ dysfunction, represents a major cause health loss and the World Health Organization (WHO) labelled sepsis as most urgent unmet medical need in 2017. The emerging biological understanding role RIPK1 has opened up an exciting opportunity to explore potent selective inhibitors effective therapeutic strategy for SIRS therapy. Herein, we have synthesized class highly dual‐mode occupying both allosteric ATP binding pockets,...
SARS-CoV-2 has still been threatening global public health with its emerging variants. Our previous work reported lead compound JZD-07 that displayed good 3CLpro inhibitory activity. Here, an in-depth structural optimization for was launched to obtain more desirable drug candidates the therapy of infection, in which 54 novel derivatives were designed and synthesized by a structure-based design strategy. Among them, 24 compounds show significantly enhanced potencies IC50 values less than 100...
Abstract Monkeypox virus (MPXV), an orthopoxvirus that has long been endemic in Africa, posed a significant global health threat since 2022. The I7L protease, highly conserved cysteine proteinase essential for replication, represents promising target broad‐spectrum antiviral drug development. Here, the first crystal structure of MPXV protease is reported, revealing its unique dimeric form and different conformations cap region nearby active site. Molecular dynamics simulations AlphaFold3...
3-Chymotrypsin-like protease (3CLpro) is a prominent target against pathogenic coronaviruses. Expert knowledge of the cysteine-targeted covalent reaction mechanism crucial to predict inhibitory potency approved inhibitors 3CLpros SARS-CoV-2 variants and perform structure-based drug design newly emerging We carried out an extensive array classical hybrid QM/MM molecular dynamics simulations explore inhibition mechanisms five well-characterized toward 3CLpro its mutants. The calculated binding...
3C-like protease (3CLpro) is indispensable for the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rendering it to be a promising druggable target treating Corona Virus Disease 2019 (COVID-19). In this study, series 2,3,5-substituted [1,2,4]-thiadiazole analogs were discovered inhibit 3CLpro as non-peptidomimetic covalent binders at sub-micromolar levels, with IC50 values ranging from 0.118 0.582 µM. The antiviral abilities these compounds also...
Abstract Sepsis, characterized with high risk of life‐threatening organ dysfunction, represents a major cause health loss and the World Health Organization (WHO) labelled sepsis as most urgent unmet medical need in 2017. The emerging biological understanding role RIPK1 has opened up an exciting opportunity to explore potent selective inhibitors effective therapeutic strategy for SIRS therapy. Herein, we have synthesized class highly dual‐mode occupying both allosteric ATP binding pockets,...