A5075664051- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- COVID-19 Clinical Research Studies
- Cholinesterase and Neurodegenerative Diseases
- Pesticide Exposure and Toxicity
- SARS-CoV-2 detection and testing
- Respiratory viral infections research
- Tuberculosis Research and Epidemiology
- Environmental Toxicology and Ecotoxicology
- PARP inhibition in cancer therapy
- Protein Structure and Dynamics
- interferon and immune responses
- Endoplasmic Reticulum Stress and Disease
- Viral Infectious Diseases and Gene Expression in Insects
- Infectious Diseases and Tuberculosis
- Cell Image Analysis Techniques
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cell death mechanisms and regulation
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Antifungal resistance and susceptibility
- Heat shock proteins research
- Transgenic Plants and Applications
- Lung Cancer Research Studies
- Infection Control and Ventilation
California Institute for Biomedical Research
2020-2025
Torrey Pines Institute For Molecular Studies
2024-2025
Scripps Research Institute
2020-2025
Tulane University
2018-2022
United States Army
2015-2016
United States Department of the Army
2010-2012
Abstract COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is virally encoded protein that essential across broad spectrum of coronaviruses with no close human analogs. PF-00835231, inhibitor, exhibited potent in vitro antiviral activity against as single agent. Here we report, design and characterization phosphate prodrug PF-07304814 to enable delivery projected sustained systemic exposure PF-00835231 inhibit coronavirus family selectivity over host targets....
Abstract The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline discovery of efficacious SARS-CoV-2 inhibitors. We screen best-in-class repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing receptor ACE2 other lung...
Abstract COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is virally encoded protein that essential across broad spectrum of coronaviruses with no close human analogs. The designed phosphate prodrug PF-07304814 metabolized to PF-00835321 which potent inhibitor in vitro coronavirus family pro, selectivity over host targets. Furthermore, PF-00835231 exhibits antiviral activity against as single agent and it additive/synergistic combination remdesivir. We...
SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified small-molecule library of 34 430 protein kinase inhibitors that were capable inhibiting cytopathic effect in human epithelial cells. These drug are various stages clinical trials. detected key proteins involved cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, DNA-damage response critical for infection. A drug-protein interaction-based...
HIV is a major driver of tuberculosis (TB) reactivation. Depletion CD4+ T cells assumed to be the basis behind TB reactivation in individuals with latent infection (LTBI) coinfected HIV. Nonhuman primates (NHPs) mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion tissue during failed reactivate TB. To investigate contribution cell relative other mechanisms SIV-induced LTBI, we used CD4R1 antibody deplete animals LTBI without lentiviral infection. The mere was...
There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by an increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) is attractive target due its homology within the coronaviral family, lack thereof toward human proteases. In this disclosure, we outline advent 3CLpro inhibitor, CMX990, bearing unprecedented trifluoromethoxymethyl ketone warhead....
Drug resistant Plasmodium falciparum parasites represent a major obstacle in our efforts to control malaria, deadly vector borne infectious disease. This situation creates an urgent need find and validate new drug targets contain the spread of Several genes associated with unfolded protein response (UPR) including Glucose-regulated Protein 78 kDa (GRP78, also known as BiP) have been deemed potential targets. We explored target GRP78, molecular chaperone that is regulator UPR, for treatment...
Many respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, few primary human stem cell-based models proximal been reported drug discovery but scaling them up to higher throughput platform remains significant challenge. As result, most screening assays are performed on commercial cell line-based 2D cultures that provide translational ability. We optimized mucociliary model SARS-CoV-2 infection, in 96-well...
The pandemic threat from newly emerging viral diseases constitutes a major unsolved issue for global health. Antiviral therapy can play an important role in treating and preventing the spread of unprecedented infections. A repository compounds exhibiting broad-spectrum antiviral activity against series different families would be invaluable asset to prepared future threats. Utilizing open innovation crowd-sourcing paradigm, we were able identify compound class diphenylureas that exhibits...
Abstract The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. A high-throughput, high-content imaging assay of human HeLa cells expressing SARS-CoV-2 receptor ACE2 was used screen ReFRAME, a best-in-class repurposing library. From nearly 12,000 compounds, we identified 66 compounds capable selectively inhibiting replication in...
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Summary Respiratory viruses (e.g. influenza, RSV, SARS etc.) attack the proximal airway and cause a wide spectrum of diseases for which we have limited therapies. To date, few primary human stem cell-based models been reported drug discovery but scaling them up to higher throughput platform remains significant challenge. Here present microscale, model SARS-CoV-2 infection, is amenable moderate-to-high screening. The recapitulates heterogeneity infection seen among different patients with...
The use of whole insect larvae as a source recombinant proteins offers more cost-effective method producing large quantities human than conventional cell-culture approaches. Human carboxylesterase 1 has been produced in and isolated from Trichoplusia ni larvae. protein was crystallized its structure solved to 2.2 Å resolution. results indicate that the larvae-produced enzyme is essentially identical cultured Sf21 cells, supporting this expression system produce enzymes for crystallization studies.
ABSTRACT There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (M pro , 3CL ) is an attractive target due its homology within the coronaviral family, lack thereof towards human proteases. In this disclosure, we outline advent inhibitor, CMX990, bearing unprecedented trifluoromethoxymethyl ketone warhead....
The atypical butyrylcholinesterase (aBuChE) from Oryzias latipes shares approximately 65% sequence similarity to both acetylcholinesterase and was studied for its capacity spontaneously reactivate following inhibition by organophosphorus nerve agents. full-length aBuChE protein expressed purified cabbage loopers (Trichoplusia ni larvae) infected with an orally active form of baculovirus. Like other cholinesterases, inhibited all G- V-type Interestingly, able undergo spontaneous reactivation...