A5054859526- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Influenza Virus Research Studies
- Escherichia coli research studies
- vaccines and immunoinformatics approaches
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- COVID-19 Pandemic Impacts
- Animal Virus Infections Studies
- Plant Virus Research Studies
- Cryospheric studies and observations
- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Advanced biosensing and bioanalysis techniques
- Diverse Aspects of Tourism Research
- Stock Market Forecasting Methods
- Protein Structure and Dynamics
- Microbial Natural Products and Biosynthesis
- Tryptophan and brain disorders
- Thermal Regulation in Medicine
University of Massachusetts Chan Medical School
2021-2025
Guangdong University of Foreign Studies
2021
Abstract Coronaviruses can evolve and spread rapidly to cause severe disease morbidity mortality, as exemplified by SARS-CoV-2 variants of the COVID-19 pandemic. Although currently available vaccines remain mostly effective against variants, additional treatment strategies are needed. Inhibitors that target essential viral enzymes, such proteases polymerases, represent key classes antivirals. However, clinical use antiviral therapies inevitably leads emergence drug resistance. In this study...
We report the results of COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. discovered noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, high-throughput structural biology chemistry. generated...
Drugs that target the main protease (Mpro) of SARS-CoV-2 are effective therapeutics have entered clinical use. Wide-scale use these drugs will apply selection pressure for evolution resistance mutations. To understand potential in Mpro, we performed comprehensive surveys amino acid changes can cause to nirmatrelvir (Pfizer), and ensitrelvir (Xocova) a yeast screen. We identified 142 mutations 177 ensitrelvir, many which not been previously reported. Ninety-nine caused apparent both...
Influenza viruses are enveloped, negative-sense single-stranded RNA covered in a dense layer of glycoproteins. Hemagglutinin (HA) accounts for 80 to 90% influenza glycoprotein and plays role host cell binding membrane fusion. While previous studies have characterized structures purified receptor-free receptor-bound HA, the effect receptor on HA organization structure virions remains unknown. Here, we used cryoelectron tomography visualize bound sialic acid mimic. Overall, did not result...
With the spread of SARS-CoV-2 throughout globe causing COVID-19 pandemic, threat zoonotic transmissions coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization inhibitor design mostly focused on these two genera. However, viruses from delta gamma genera also infect mammals pose a potential transmission threat. Here, we determined inhibitor-bound crystal structures main protease (Mpro) delta-CoV porcine HKU15...
Abstract Drugs that target the main protease (M pro ) of SARS-CoV-2 are effective therapeutics have entered clinical use. Wide-scale use these drugs will apply selection pressure for evolution resistance mutations. To understand potential in M , we performed comprehensive surveys amino acid changes can cause a yeast screen to nirmatrelvir (contained drug Paxlovid), and ensitrelvir (Xocova) is currently phase III trials. The most impactful mutation (E166V) recently reported multiple viral...
Abstract Coronaviruses, as exemplified by SARS-CoV-2, can evolve and spread rapidly to cause severe disease morbidity mortality. Direct acting antivirals (DAAs) are highly effective in decreasing burden especially when they target essential viral enzymes, such proteases polymerases, demonstrated HIV-1 HCV most recently SARS-CoV-2. Optimization of these DAAs through iterative structure-based drug design has been shown be critical. Particularly, the evolutionarily conserved molecular...
This paper examines the determinants of tourism stock returns in China from October 25, 2018, to 21, 2020, including COVID-19 era. We propose four deep learning prediction models based on Back Propagation Neural Network (BPNN): Quantum Swarm Intelligence Algorithms (QSIA), Step Fruit-Fly Optimization Algorithm (QSFOA), Particle (QPSO) and Genetic (QGA). Firstly, rough dataset is used reduce dimension indices. Secondly, number neurons multilayer BPNN optimized by QSIA, QSFOA, QPSO, QGA,...
Influenza viruses are enveloped, negative sense single-stranded RNA covered in a dense layer of glycoproteins. Hemagglutinin (HA) accounts for 80-90% influenza glycoprotein and plays role host cell binding membrane fusion. While previous studies have characterized structures receptor-free receptor-bound HA vitro, the effect receptor on organization structure virions remains unknown. Here, we used cryo-electron tomography (cryoET) to visualize bound sialic acid mimic. Overall, did not result...
Abstract With the spread of SARS-CoV-2 throughout globe to cause COVID-19 pandemic, threat zoonotic transmissions coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization inhibitor design mostly focused on these two genera. However, viruses from delta gamma genera also infect mammals pose potential transmission threat. Here, we determined inhibitor-bound crystal structures main protease (M pro ) delta-CoV...
SUMMARY Pattern recognition of bacterial products by host receptors is essential for innate immunity in many metazoans. Curiously, the nematode lineage lost canonical mechanisms pattern recognition. Whether other immune evolved their place not known. Here, we characterize first receptor and its natural ligand Caenorhabditis elegans . We show that C. nuclear hormone NHR-86/HNF4 senses phenazine-1-carboxamide (PCN), a metabolite produced pathogenic strains Pseudomonas aeruginosa PCN binds to...
Summary Influenza viruses pose severe public health threats; they cause millions of infections and tens thousands deaths annually in the US. are extensively pleomorphic, both shape size as well organization viral structural proteins. Analysis influenza morphology ultrastructure can help elucidate structure-function relationships aid therapeutics vaccine development. While cryo-electron tomography (cryoET) depict 3D pleomorphic influenza, low signal-to-noise ratio inherent to cryoET extensive...