A5100320643- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Long-Term Effects of COVID-19
- Viral Infections and Vectors
- Virus-based gene therapy research
- SARS-CoV-2 detection and testing
- Monoclonal and Polyclonal Antibodies Research
- Infectious Diseases and Tuberculosis
- Antifungal resistance and susceptibility
- Viral Infections and Immunology Research
- Bacteriophages and microbial interactions
- interferon and immune responses
- Bacillus and Francisella bacterial research
- Antimicrobial Resistance in Staphylococcus
- Microbial Metabolic Engineering and Bioproduction
- Ion Transport and Channel Regulation
- Microbial Metabolism and Applications
- Vector-borne infectious diseases
- Ocular Infections and Treatments
- Receptor Mechanisms and Signaling
- Acute Kidney Injury Research
Westlake University
2020-2025
State Key Laboratory of Respiratory Disease
2024
Guangzhou Medical University
2024
First Affiliated Hospital of Guangzhou Medical University
2024
Zhejiang University
2024
Wuhan University
2024
National Institute for Health and Care Excellence
2024
Nankai University
2024
State Key Laboratory of Medicinal Chemical Biology
2024
Academy of Military Medical Sciences
2024
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and new coronavirus (SARS-CoV-2) that causing serious disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in presence neutral amino acid transporter B0AT1 with or without binding domain (RBD) surface spike glycoprotein (S protein) SARS-CoV-2, both at an overall resolution 2.9 angstroms, a local 3.5 angstroms...
Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on receptor binding domain (RBD) Spike (S) protein but also across full protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency both pseudotyped SARS-CoV-2 does bind RBD....
Abstract Angiotensin-converting enzyme 2 (ACE2) has been suggested to be the cellular receptor for new coronavirus (2019-nCoV) that is causing disease 2019 (COVID-19). Like other coronaviruses such as SARS-CoV, 2019-nCoV uses binding domain (RBD) of surface spike glycoprotein (S protein) engage ACE2. We most recently determined structure full-length human ACE2 in complex with a neutral amino acid transporter B 0 AT1. Here we report cryo-EM bound RBD at an overall resolution 2.9 Å presence...
Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable disrupting proper interaction between the receptor binding domain (RBD) viral spike (S) protein and angiotensin converting enzyme (ACE2). However, structural basis their potent neutralizing activity remains unclear....
Abstract The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, P.1), SARS-CoV HCoV-NL63, without markedly affecting physiological...
The COVID-19 pandemic has caused millions of infections and deaths resulted in unprecedented international public health social economic crises. As SARS-CoV-2 spread across the globe its impact became evident, development safe effective vaccines a priority. Outlining processes used to establish support conduct phase 3 randomized clinical trials that led rapid emergency use authorization approval several is major significance for current future response efforts.
Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, broad-spectrum neutralization capacity against SARS-CoV-2 variants concern (VOCs) and SARS-CoV, well related bat pangolin viruses. 5817 can hardly compete six classes...
Background Although the Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been available for more than 75 years, one third of world's population is still infected with Mycobacterium and approximately 2 million people die TB every year. To reduce this immense burden, a clearer understanding functional genes underlying action BCG development new vaccines are urgently needed. Methods Findings Comparative genomic analysis 19 M. complex strains showed that underwent repeated...
Abstract The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused the receptor binding domain (RBD) Spike (S) protein, whereas vulnerable epitopes and functional mechanism non-RBD regions are poorly understood. Here we isolated characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting N-terminal...
Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant tightly associated with human diseases including cancers. Here, we report the cryo-EM structure WLS in complex Wnt3a, most widely studied Wnt, at 2.2 Å resolution. The domain bears a GPCR fold, core cavity and lateral opening. Wnt3a interacts multiple interfaces, lipid moiety on traversing...
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants concern, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) has aroused concerns over their increased infectivity transmissibility, as well decreased sensitivity to SARS-CoV-2-neutralizing antibodies (NAbs) the current coronavirus disease 2019 (COVID-19) vaccines. Such exigencies call for development pan-sarbecovirus vaccines or inhibitors combat circulating...
In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit replication in human cells. Notably, nucleosides tailored at ribose 2'-position outperform those modified nucleobase. Our vivo validation using...
The world is in the midst of coronavirus disease 2019 (COVID-19) pandemic. Interleukin 6 (IL-6) inhibitor (tocilizumab) had been suggested for treatment acute respiratory distress syndrome (ARDS) patients based on concept "cytokine storm" COVID-19. However, we still lack reliable studies to verify COVID-19 pneumonia. Furthermore, IL-6 has potential hazards inducing infectious diseases. efficacy monoclonal antibody-directed therapy remains be fully evaluated.
Abstract The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel bnAbs against other variants concern (VOCs) elicited vaccination adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated human longitudinal antibody responses following demonstrated how evolved over time. A...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance VOCs bring unprecedented challenges epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current has surprising tolerance mutations adjacent or within its interaction epitope. Cryo-electron microscopy structure showed 2G1 bound tip receptor binding domain (RBD) spike protein...
Abstract The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis reported spike protein antibodies, counting epitopes genotypes these antibodies. We further comprehensively analyzed impact mutations on antibody classified antibodies according their binding patterns. found that H-RBD class were...
The solute carrier 13 (SLC13) family comprises electrogenic sodium ion-coupled anion cotransporters, segregating into ion-sulfate cotransporters (NaSs) and ion-di- and-tricarboxylate (NaDCs). NaS1 NaDC1 regulate sulfate homeostasis oxidative metabolism, respectively. deficiency affects murine growth fertility, while urinary citrate calcium nephrolithiasis. Despite their importance, the mechanisms of substrate recognition transport remain insufficiently characterized. In this study, we...
Heteromeric amino acid transporters (HATs), including y + LAT1-4F2hc complex, are responsible for transporting acids across membranes, and mutations in LAT1 cause lysinuric protein intolerance (LPI), a hereditary disorder characterized by defective cationic transport. The relationship between LPI specific has yet to be fully understood. In this study, we the function of complex mammalian cells determined cryo-EM structures human two distinct conformations: apo state an inward-open...
Abstract Sodium-Potassium Pump (Na + /K -ATPase, NKA) is an ion pump that generates electrochemical gradient of sodium and potassium ions across the plasma membrane by hydrolyzing ATP. During each Post-Albers cycle, NKA exchanges three cytoplasmic for two extracellular through alternating changes between E1 E2 states. Hitherto, several steps remained unknown during complete working cycle NKA. Here, we report cryo-electron microscopy (cryo-EM) structures recombinant human (hNKA) in distinct...