A5081846726- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- Mosquito-borne diseases and control
- IL-33, ST2, and ILC Pathways
- Crystallization and Solubility Studies
- RNA Research and Splicing
- Synthesis and Catalytic Reactions
- RNA modifications and cancer
- Biochemical and Molecular Research
- Viral Infectious Diseases and Gene Expression in Insects
- interferon and immune responses
- Viral Infections and Vectors
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Wound Healing and Treatments
- Immune Cell Function and Interaction
- Insect symbiosis and bacterial influences
- Asymmetric Hydrogenation and Catalysis
- Eosinophilic Esophagitis
- Cardiac Ischemia and Reperfusion
- Monoclonal and Polyclonal Antibodies Research
- Advanced Glycation End Products research
- Virus-based gene therapy research
- X-ray Diffraction in Crystallography
Ningxia University
2025
China Medical University
2025
First Hospital of China Medical University
2025
Ministry of Education of the People's Republic of China
2021-2024
Nanjing University
2012-2024
Jiangsu University
2014-2024
Southwest Jiaotong University
2023-2024
First Affiliated Hospital of Kunming Medical University
2024
Nanjing Drum Tower Hospital
2024
Institute of Life Sciences
2024
The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key enzyme, which extensively digests CoV replicase polyproteins essential for viral replication and transcription, making it an attractive target antiviral drug development. However, the molecular mechanism how Mpro SARS-CoV-2 polyproteins, releasing nonstructural proteins (nsps), its substrate specificity remain largely unknown. Here, we determine high-resolution structures in resting state,...
Recently we demonstrated that the effects of beta 2-adrenoceptor (AR) stimulation to augment Ca2+ current (ICa), cytosolic (Cai) transients, and contractility in rat ventricular myocytes are largely dissociated from its effect increase cellular cAMP levels. This result suggested 2ARs might be coupled signaling pathways other than Gs alpha-mediated activation adenylyl cyclase. Here show pertussis toxin (PTX) pretreatment specifically potentiates responses heart cells 2AR but not 1AR...
While an age-associated diminution in myocardial contractile response to beta-adrenergic receptor (beta-AR) stimulation has been widely demonstrated occur the context of increased levels plasma catecholamines, some critical mechanisms that govern beta-AR signaling must still be examined aged hearts. Specifically, contribution subtypes (beta1 versus beta2) overall reduction with aging is unknown. Additionally, whether G protein-coupled kinases (GRKs), which mediate desensitization, or...
Significance SAMHD1 is a dNTPase that depletes the cellular dNTP pool to inhibit replication of retroviruses, including HIV-1. The activity also enables enzyme be major regulator levels in mammalian cells, addition implicated pathogenesis chronic lymphocytic leukemia (CLL) and Aicardi Goutières syndrome (AGS). Here we present extensive structural enzymatic data reveal how activated regulated via combined actions GTP all dNTPs. Our work establishes complete spectrum nucleotide binding...
The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. high number spike mutations responsible for broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present cryo-electron microscopy structure ACE2-bound spike. Comparison to previous structures explains how escapes these therapeutics. Secondly, report Omicron, Delta, wild-type spikes bound a patient-derived Fab fragment (510A5), which provides direct evidence where...
The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of booster vaccination disease 2019 (COVID-19). inactivated vaccine, CoronaVac, is most widely supplied COVID-19 vaccine globally. Whether CoronaVac elicited adaptive responses that cross-recognize SARS-CoV-2 concern (VoCs) among 77 healthy subjects receiving third dose were explored. After boost, remarkable elevated spike-specific IgG IgA...
The accessory protein Orf6 is uniquely expressed in sarbecoviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which an ongoing pandemic. SARS-CoV-2 antagonizes host interferon signaling by inhibition of mRNA nuclear export through its interactions with the ribonucleic acid 1 (Rae1)-nucleoporin 98 (Nup98) complex. Here, we confirmed direct tight binding to Rae1-Nup98 complex, competitively inhibits RNA binding. We determined crystal structures both and SARS-CoV-1...
The recent explosive outbreak of Zika virus (ZIKV) infection has been reported in South and Central America the Caribbean. Neonatal microcephaly associated with ZIKV already caused a public health emergency international concern. No specific vaccines or drugs are currently available to treat infection. helicase, which plays pivotal role viral RNA replication, is an attractive target for therapy. We determined crystal structures helicase-ATP-Mn2+ helicase-RNA. This first structure any...
Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase possibility of immune escape, challenging present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 13G9, with high neutralizing potency blocking authentic virus display remarkable efficacy against B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 13G9 both recognize steric region S470-495 on RBD, overlapping...
Tripartite motif protein isoform 5 alpha (TRIM5α) is a potent antiviral that restricts infection by HIV-1 and other retroviruses. TRIM5α recognizes the lattice of retrovirus capsid through its B30.2 (PRY/SPRY) domain in species-specific manner. Upon binding, induces premature disassembly viral activates downstream innate immune response. We have determined crystal structure rhesus PRY/SPRY reveals essential features for binding. Combined cryo-electron microscopy biochemical data show...
Abstract The X-ray free-electron laser (XFEL) allows the analysis of small weakly diffracting protein crystals, but has required very many crystals to obtain good data. Here we use an XFEL determine room temperature atomic structure for smallest cytoplasmic polyhedrosis virus polyhedra yet characterized, which failed solve at a synchrotron. These microcrystals, roughly micron across, accrue within infected cells. We new physical model diffraction, better estimates experimental signal,...
Significance Guanylate-binding proteins (GBPs) belong to interferon-inducible GTPases and mediate a broad spectrum of innate immune responses against various pathogens. Their protective functions require oligomerization induced by nucleotide binding and/or catalysis, but the actual molecular mechanisms are still elusive. Here, we report crystal structures human GBP5 (hGBP5) in both its nucleotide-free state nucleotide-bound state, as well GBP2 (hGBP2). We show that hGBP5 forms closed...