A5069232388- HIV/AIDS drug development and treatment
- Hepatitis C virus research
- Biochemical and Molecular Research
- HIV Research and Treatment
- Mosquito-borne diseases and control
- CRISPR and Genetic Engineering
- Pneumocystis jirovecii pneumonia detection and treatment
- Liver Disease Diagnosis and Treatment
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Viral Infections and Immunology Research
Emory University
2019-2024
Children's Healthcare of Atlanta
2021-2024
ABSTRACT Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents which potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into Phase 2a clinical trials. Previous cell culture based breakthrough assays identified the (Y99H/A128T IN) variant that confers substantial resistance to this inhibitor. Here, we...
ABSTRACT Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents that potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into phase 2a clinical trials. Previous cell culture-based breakthrough assays identified the (Y99H/A128T IN) variant confers substantial resistance to this inhibitor. Here, we have...
Hepatitis C virus (HCV) nucleoside inhibitors display pan-genotypic activity, a high barrier to the selection of resistant virus, and are some most potent direct-acting agents with durable sustained virologic response in humans. Herein, we report, discovery β-d-2′-Br,2′-F-uridine phosphoramidate diastereomers 27 28, as nontoxic anti-HCV agents. Extensive profiling these two phosphorous was performed select one for in-depth preclinical profiling. The 5′-triphosphate formed from...
Yellow fever virus (YFV) is a human Flavivirus reemerging in parts of the world. While vaccine available, large outbreaks have recently occurred Brazil and certain African countries. Development an effective antiviral against YFV crucial, as there no available drug YFV. We identified several novel nucleoside analogs with potent activity 50% concentration (EC50) values between 0.25 1 μM selectivity indices over 100 culture.
We present a newly developed synthetic route to 2-bromo-2-fluoro ribolactone based on our published 2-chloro-2-fluoro synthesis. Stereoselective fluorination is key controlling the 2-diastereoselectivity. also report substantially improved glycosylation reaction with both and sugars. These improvements allowed us prepare 2'-dihalo nucleosides 13 14 in an overall 15-20% yield.
Abstract Nucleoside analogs are the backbone of antiviral therapies. Drugs from this class undergo processing by host or viral kinases to form active nucleoside triphosphate species that selectively inhibits polymerase. It is central hypothesis analog must be a favorable substrate for polymerase and precursor satisfactory inhibit replication. Herein, free energy perturbation (FEP) was used predict affinity both enzymes. Several uridine 5’‐monophosphate prodrug known hepatitis C virus (HCV)...