A5028269400- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- Bacillus and Francisella bacterial research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Crystallization and Solubility Studies
- Lipid Membrane Structure and Behavior
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- X-ray Diffraction in Crystallography
- Bacteriophages and microbial interactions
- Viral Infections and Outbreaks Research
Chinese Academy of Sciences
2024
Shanghai Institute of Materia Medica
2024
Institut Pasteur of Shanghai
2020-2022
University of Chinese Academy of Sciences
2020-2022
Communication University of China
2021
Abstract The SARS-CoV-2 Delta variant is currently the dominant circulating strain in world. Uncovering structural basis of enhanced transmission and altered immune sensitivity particularly important. Here we present cryo-EM structures revealing two conformational states spike S/ACE2 complex four states. Our analysis suggests that RBD destabilizations lead to population shift towards more RBD-up S1 destabilized fusion-prone state, beneficial for engagement with ACE2 shedding S1. Noteworthy,...
Abstract The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development treating COVID-19. Here, we report the identification and characterization two groups mouse neutralizing monoclonal (MAbs) targeting receptor-binding domain (RBD) on spike (S) protein. MAbs 2H2 3C1, representing antibody groups, respectively, bind distinct epitopes compatible in...
Abstract The emergence of SARS-CoV-2 Kappa and Beta variants with enhanced transmissibility resistance to neutralizing antibodies has created new challenges for the control ongoing COVID-19 pandemic. Understanding structural nature spike (S) proteins their association ACE2 is significant importance. Here we present two cryo-EM structures each spikes in open open-prone transition states. Compared wild-type (WT) or G614 spikes, variant appear more untwisted/open especially Beta, display a...
Abstract Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here preclinical development yeast-produced receptor-binding domain (RBD)-based recombinant protein vaccines. found that monomeric RBD could be efficiently produced as a secreted from transformed Pichia pastoris ( P. ) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level neutralizing antibodies in mice....
The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern threatens the efficacy currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs defining their epitopes. Here, we isolate 9 mouse raised against spike protein a prototype strain evaluate potency towards panel variants, including B.1.1.7, B.1.351, B.1.617.1, B.1.617.2. By using...
An essential step for SARS-CoV-2 infection is the attachment to host cell receptor by its Spike receptor-binding domain (RBD). Most of existing RBD-targeting neutralizing antibodies block motif (RBM), a mutable region with potential generate neutralization escape mutants. Here, we isolated and structurally characterized non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages RBD at an epitope distal RBM KD 5.6 nM, neutralizes including current Variants Concern...
Abstract The SARS-CoV-2 Omicron variant exhibits striking immune evasion and is spreading globally at an unprecedented speed. Understanding the underlying structural basis of high transmissibility greatly enhanced importance. Here through cryo-EM analysis, we present both closed open states spike, which appear more compact than counterparts G614 strain, potentially related to substitution induced protomer-protomer S1-S2 interactions. state showing dominant population may indicate a...
Neutralizing antibodies (nAbs) play an important role against SARS-CoV-2 infections. Previously, we have reported one potent receptor binding domain (RBD)-binding nAb Ab08 the prototype and a panel of variants, but showed much less efficacy variants harboring L452R mutation. To overcome antibody escape caused by mutation, generated several structure-based derivatives. One derivative, Ab08-K99E, displayed mostly enhanced neutralizing potency Delta pseudovirus bearing mutation compared to...
Abstract The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 which are located within receptor binding domain (RBD). Consequently, is able to extensively escape existing neutralizing antibodies and may therefore compromise efficacy current vaccines based original strain, highlighting importance urgency developing effective against Omicron. Here we report rapid generation evaluation an mRNA...
The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 which are located within receptor binding domain (RBD). Consequently, is able to extensively escape existing neutralizing antibodies and may therefore compromise efficacy current vaccines based original strain, highlighting importance urgency developing effective against Omicron. Here we report rapid generation evaluation an mRNA vaccine...
Abstract Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for ongoing disease 2019 (COVID-19) pandemic. Currently, there no vaccine available preventing SARS-CoV-2 infection. Like closely related (SARS-CoV), also uses its receptor-binding domain (RBD) on spike (S) protein to engage host receptor, human angiotensin-converting enzyme (ACE2), facilitating subsequent viral entry. Here we report immunogenicity and potential of RBD...
The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as vaccine antigen. emergence several novel variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison RBD, S1, and S ectodomain trimer (S-trimer) antigens evaluated their induction...
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in catastrophic damage worldwide. Accordingly, the development of powerful, safe, easily accessible vaccines with long-term effectiveness is understood as an urgently needed countermeasure against this ongoing pandemic. Guided strong promise using AAVs, we here designed, optimized, and developed AAV-based (including AAV-RBD(max), AAV-RBD(wt), AAV-2xRBD,...
Abstract The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome 2 (SARS-CoV-2). current SARS-CoV-2 vaccines are based on spike (S) protein, S1 subunit, or receptor-binding domain (RBD) of prototype strain. Emergence several novel variants has raised concern about potential immune escape. In this study, we performed an immunogenicity comparison ancestral RBD, S1, and S ectodomain trimer (S-trimer) antigens tested the efficacy these against...