A5008792226- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- Chemical Synthesis and Analysis
- Phosphodiesterase function and regulation
- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- COVID-19 Clinical Research Studies
- Pharmacological Receptor Mechanisms and Effects
- Phenothiazines and Benzothiazines Synthesis and Activities
- HIV/AIDS drug development and treatment
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Synthesis and Catalytic Reactions
- Synthesis and Biological Evaluation
- Neurotransmitter Receptor Influence on Behavior
- Cholinesterase and Neurodegenerative Diseases
- Catalytic C–H Functionalization Methods
- Carbohydrate Chemistry and Synthesis
- Quinazolinone synthesis and applications
- Crystallization and Solubility Studies
- Cannabis and Cannabinoid Research
- Click Chemistry and Applications
- X-ray Diffraction in Crystallography
- Cancer Treatment and Pharmacology
- Pulmonary Hypertension Research and Treatments
Shanghai Institute of Materia Medica
2016-2025
Chinese Academy of Sciences
2016-2025
University of Chinese Academy of Sciences
2018-2025
Nanjing University of Chinese Medicine
2022-2025
State Key Laboratory of Drug Research
2022-2025
China-Japan Friendship Hospital
2024
Beijing Ditan Hospital
2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2024
Shanghai Clinical Research Center
2021-2022
Xinjiang Technical Institute of Physics & Chemistry
2021-2022
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), has become a global crisis. Replication SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, target antiviral drug remdesivir. Here we report cryo-electron microscopy structure RdRp, both in apo form at 2.8-angstrom resolution and complex with 50-base template-primer remdesivir 2.5-angstrom resolution. reveals that partial double-stranded template is inserted...
Abstract The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) urgently needs an effective cure. 3CL protease (3CL pro ) is a highly conserved cysteine proteinase that indispensable for replication, providing attractive target developing broad-spectrum antiviral drugs. Here we describe the discovery myricetin, flavonoid found in many food sources, as non-peptidomimetic and covalent inhibitor SARS-CoV-2 . Crystal structures...
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, origin excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like in vitro vivo. 2-E proteins were found form a type pH-sensitive cation channels bilayer lipid membranes. As observed SARS-CoV-2-infected cells, heterologous expression induced rapid cell death various susceptible...
BackgroundSimnotrelvir is an oral 3-chymotrypsin–like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy a phase 1B trial.MethodsIn this 2–3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate disease 2019 (Covid-19) onset of symptoms within the past 3 days 1:1 ratio receive 750 mg simnotrelvir plus 100 ritonavir or placebo twice daily for 5...
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
Abstract Human infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause disease 19 (COVID-19) and there is currently no cure. The 3C-like protease (3CLpro), a highly conserved indispensable for replication of coronaviruses, promising target development broad-spectrum antiviral drugs. To advance the speed drug discovery development, we investigated inhibition SARS-CoV-2 3CLpro by natural products derived from Chinese traditional medicines. Baicalin baicalein were...
For proof-of-concept of halogen bonding in drug design, a series halogenated compounds were designed based on lead structure as new inhibitors phosphodiesterase type 5. Bioassay results revealed good correlation between the measured bioactivity and calculated bond energy. Our X-ray crystal structures verified existence predicted bonds, demonstrating that is an applicable tool design should be routinely considered optimization.
Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates protein–protein interaction (PPI) between catalytic subunit EZH2 EED. Deregulated PRC2 is intimately involved in tumorigenesis progression, making it an invaluable target for epigenetic cancer therapy. However, until now, there have been no reported small molecule compounds targeting EZH2-EED interactions. In...
VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose the three phase I studies was to evaluate safety, tolerability, and pharmacokinetics single multiple ascending doses in healthy subjects, as well effect food on safety VV116. Three were launched sequentially: Study 1 (single ascending-dose study, SAD), 2 (multiple MAD), 3 (food-effect FE). A total 86 subjects enrolled studies. tablets or placebo administered per protocol requirements. Blood samples...
SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CL
The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. replication requires the viral RNA-dependent RNA polymerase (RdRp), direct target antiviral drug, Remdesivir. Here we report structure RdRp either in apo form or complex with 50-base template-primer and Remdesivir at resolution range 2.5-2.8 Å. reveals that partial double-stranded template is inserted into central channel where incorporated first replicated base pair terminates chain...
A novel synthetic route for making (−)-CBD and its derivatives bearing various C4′-side chains is developed by a late-stage diversification method. Starting from commercially available phloroglucinol, the key intermediate (−)-CBD-2OPiv-OTf efficiently regioselectively prepared further undergoes Negishi cross-coupling to furnish (−)-CBD. This approach allowed an efficient synthesis of in five-step total 52% yield on 10 g scale. Furthermore, chain with this method can be realized wide range.
Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome 2 (SARS-CoV-2). We evaluated safety, tolerability, pharmacokinetics dose escalations simnotrelvir alone or with ritonavir (simnotrelvir simnotrelvir/ritonavir) healthy subjects, as well food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence...
Abstract During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from FDA, some side effect concerns emerged, possible agents are still limited, resulting in optimized drug development becoming urgent requirement. An remdesivir derivative, VV116, reported to promising effects against positive...
We present an improved copper-catalyzed cyclization for efficient synthesis of benzimidazoles from