A5102723378- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Advanced biosensing and bioanalysis techniques
- Studies on Chitinases and Chitosanases
- COVID-19 Clinical Research Studies
- Single-cell and spatial transcriptomics
- Research on Leishmaniasis Studies
- Immunotherapy and Immune Responses
- Pneumocystis jirovecii pneumonia detection and treatment
- Molecular Biology Techniques and Applications
- Animal Virus Infections Studies
- Influenza Virus Research Studies
- Carbohydrate Chemistry and Synthesis
- Enzyme Structure and Function
- Vaccine Coverage and Hesitancy
- Biochemical and Molecular Research
University of North Carolina at Chapel Hill
2023-2025
Yale University
2023
Biomedical Research Institute
2023
Texas Biomedical Research Institute
2023
Baxter (United States)
2023
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...
Despite their widespread impact on human health, there are no approved drugs for combating alphavirus infections. The heterocyclic β-aminomethyl vinyl sulfone RA-0002034 (
Alphaviruses are mosquito-borne RNA viruses that pose a significant public health threat, with no FDA-approved antiviral therapeutics available. The non-structural protein 2 helicase (nsP2hel) is an enzyme involved in unwinding dsRNA essential for alphavirus replication. This study reports the discovery and optimization of first-in-class oxaspiropiperidine inhibitors targeting nsP2hel. Structure-activity relationship (SAR) studies identified potent cyclic sulfonamide analogs nanomolar...
RA-0003022 (3) was identified as a high-quality covalent chemical probe for Chikungunya nsP2 cysteine protease (nsP2pro). Isoxazole 3 covalently captured the active site C478 and inactivated enzyme with kinact/Ki ratio of 6000 M-1s-1. A negative control analog RA-0025453 (4) retained warhead but demonstrated >100-fold decrease in inhibition. Isoxazoles 4 were stable cross wide range pH solution upon prolonged storage solids. The inactive across panel 23 human viral proteases remarkable...
RNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary of novel variants relative well-studied genotypes epidemic viruses. Competition assays are an effective rigorous system which assess genotypes. However, it challenging cheaply distinguish quantify differences between very similar Here, we describe a protocol using reverse...
<title>Abstract</title> Inactivated whole virus SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide (Alum) are among the most widely used COVID-19 globally and have been critical to pandemic response. Although these protective against homologous infection in healthy recipients, emergence of novel variants presence large zoonotic reservoirs provide significant opportunities for vaccine breakthrough, which raises risk adverse outcomes including vaccine-associated enhanced respiratory...