A5067798579- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Viral Infections and Immunology Research
- Influenza Virus Research Studies
- Legume Nitrogen Fixing Symbiosis
- Salmonella and Campylobacter epidemiology
- Polyamine Metabolism and Applications
- Monoclonal and Polyclonal Antibodies Research
- CRISPR and Genetic Engineering
- interferon and immune responses
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Bioinformatics and Genomic Networks
- Bacillus and Francisella bacterial research
- Genomics and Phylogenetic Studies
- Respiratory viral infections research
- Mosquito-borne diseases and control
- Microbial Inactivation Methods
- Heat shock proteins research
- vaccines and immunoinformatics approaches
University of North Carolina at Chapel Hill
2020-2024
UNC Lineberger Comprehensive Cancer Center
2024
Segeberger Kliniken
2024
Gryphon Scientific (United States)
2023
Oak Ridge Institute for Science and Education
2023
Public Health Department
2022
Rochester Institute of Technology
2017-2020
Coronaviruses are prone to transmission new host species, as recently demonstrated by the spread humans of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent disease 2019 (COVID-19) pandemic1. Small animal models that recapitulate SARS-CoV-2 needed urgently for rapid evaluation medical countermeasures2,3. cannot infect wild-type laboratory mice owing inefficient interactions between viral spike protein and mouse orthologue human receptor, angiotensin-converting...
Abstract Coronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease desperately needed rapidly evaluate medical countermeasures (MCMs). cannot infect wildtype laboratory mice due inefficient interactions between viral spike (S) protein and murine ortholog human receptor, ACE2. We used reverse genetics remodel S mACE2 binding interface resulting in a...
Group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. Here, we evaluate the mechanisms of cross-sarbecovirus protective immunity, currently less clear yet important for pan-sarbecovirus vaccine development, using a panel alphavirus-vectored vaccines covering bat to human strains. While vaccination does not prevent virus replication, it protects against lethal heterologous disease outcomes both severe acute respiratory syndrome coronavirus 2...
The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development countermeasures provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive...
Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice cynomolgus macaques from severe disease. The mechanisms of NTD antibody-mediated protection are unknown. Here we show Fc mediate (non-nAb) MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not...
Abstract The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness showed less efficient via airborne route compared SARS-CoV-2 in hamsters. was potently inhibited by US Food Drug Administration approved drugs,...
Despite the wide availability of several safe and effective vaccines that prevent severe COVID-19, persistent emergence acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern (VOCs) can evade vaccine-elicited immunity remains a global health concern. In addition, SARS-CoV-2 VOCs therapeutic monoclonal antibodies underscores need for additional, variant-resistant treatment strategies. Here, we characterize antiviral activity GS-5245, obeldesivir (ODV), an oral prodrug parent...
Significance A potential outbreak of swine acute diarrhea syndrome coronavirus (SADS-CoV) in the human population could be devastating. Using genomewide CRISPR knockout screening, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection, uncovering a novel antiviral target CoV infection. The PLAC8-related pathway may also have implications other infections. Given ability to infect primary cultures without adaptation, our findings lay foundation...
Mature DENVs represent the dominant form in vivo and are target for vaccine development. Here, we used multiple strategies, including protein engineering natural directed evolution to generate DENV1, -2, -3, -4 variants that highly mature without compromising replication efficiency compared parental strains.
Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, emergence SARS-CoV-2 variants concern (VOC) partially evade vaccine immunity remains a global health concern. In addition, highly mutated neutralization-resistant VOCs such as BA.1 BA.5 or fully (1) many therapeutic monoclonal antibodies in clinical use underlines need for additional treatment strategies. Here, we characterize antiviral activity GS-5245, Obeldesivir (ODV), an oral...
Abstract Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these are protective against homologous coronavirus infection, emergence of novel variants and presence large zoonotic reservoirs harboring heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises risk adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female...
ABSTRACT Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be yet it protected mice cynomolgus macaques from severe disease. The mechanisms of this antibody-mediated protection are unknown. Here we show Fc mediate (non-nAb) MA10 viral challenge in mice. Though non-nAb infusion did not suppress infectious...
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Traditional informatics in comparative genomics work only with static representations of biomolecules (i.e., sequence and structure), thereby ignoring the molecular dynamics (MD) proteins that define function cell. A approach applied to MD would connect this very short timescale process, defined femtoseconds, one longest universe: evolution measured millions years. Here, we leverage advances graphics-processing-unit-accelerated simulation software develop a method analysis visualization can...
The application of statistical methods to comparatively framed questions about the molecular dynamics (MD) proteins can potentially enable investigations biomolecular function beyond current sequence and structural in bioinformatics. However, chaotic behavior single MD trajectories requires inference that is derived from large ensembles simulations representing comparative functional states a protein under investigation. Meaningful interpretation such complex forms big data poses serious...
The aminotransferase gene family in the model plant Arabidopsis thaliana consists of 44 genes, eight which are suggested to be alanine aminotransferases. One putative aminotransferases At3g08860, was attributed function alanine:glyoxylate aminotransferase/β-alanine:pyruvate based on analysis expression networks and homology other β-alanine plants. It earlier demonstrated that At3g08860 is specifically upregulated response osmotic stress, but not stresses (β-alanine an osmoprotectant plants)....
The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development therapeutic countermeasures provide broad protection against and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine recognize conserved epitopes in receptor binding domain (RBD) femtomolar affinities. Longitudinal analysis revealed progressive...
Pulmonary anthrax caused by exposure to inhaled Bacillus anthracis, the most lethal form of disease, is a continued military and public health concern for United States. The vaccine AV7909, consisting licensed drug substance AVA adjuvanted with CpG7909, induces high levels toxin neutralizing antibodies in healthy adults using fewer doses than AVA. This study compares ability one- or two-dose regimens AV7909 induce protective immune response guinea pigs challenged dose aerosolized B....
The head of Salmonella virus SPN3US is composed ~50 different proteins and unusual because within its packaged genome there a mass (>40 MDa) ejection or E that enter the cell. assembly mechanisms this complex structure are poorly understood. Previous studies showed eight in mature had been cleaved by prohead protease. In study, we present characterization protease mutants using transmission electron microscopy spectrometry. absence protease, formation was severely impeded proheads...
The association between low-frequency HIV-1 drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this using NGS methods that accurately sample DRMs.
SARS-CoV-2 (the causative agent of COVID-19) is a major public health threat and one two related coronaviruses that have caused epidemics in modern history. A method screening potential infectible hosts for preemergent future emergent would aid mounting rapid response intervention strategies during emergence events.
A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03107-5
Two group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. The mechanisms of cross protection driven by the sarbecovirus spike, a dominant immunogen, are less clear yet critically important for pan-sarbecovirus vaccine development. We evaluated cross-sarbecovirus protective immunity using panel alphavirus-vectored vaccines covering bat to human strains. While vaccination did not prevent virus replication, it protected against lethal...