A5009818960- Mosquito-borne diseases and control
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Computational Drug Discovery Methods
- Chemical synthesis and alkaloids
- Autophagy in Disease and Therapy
- SARS-CoV-2 and COVID-19 Research
- Synthesis and Catalytic Reactions
- Viral Infections and Vectors
- Calcium signaling and nucleotide metabolism
- Alkaloids: synthesis and pharmacology
- Advanced Synthetic Organic Chemistry
- Wine Industry and Tourism
- Bone health and treatments
- Virology and Viral Diseases
- Phagocytosis and Immune Regulation
- COVID-19 Clinical Research Studies
- Machine Learning in Bioinformatics
- Consumer Behavior in Brand Consumption and Identification
- Plant Virus Research Studies
- Heterotopic Ossification and Related Conditions
- HIV/AIDS drug development and treatment
- TGF-β signaling in diseases
- Culinary Culture and Tourism
- Synthesis and Biological Evaluation
National Center for Advancing Translational Sciences
2018-2025
National Institutes of Health
2018-2025
Indiana University Bloomington
2003-2006
The re-emergence of Zika virus (ZIKV) and Ebola (EBOV) poses serious continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, anti-protozoal agent, potently inhibits ZIKV EBOV infection with a low nanomolar half maximal inhibitory concentration (IC50) in vitro potent activity vivo. Two mechanisms action emetine are identified: inhibition NS5 polymerase disruption lysosomal function. Emetine also entry. Cephaeline,...
Understanding the SARS-CoV-2 virus' pathways of infection, virus–host–protein interactions, and mechanisms virus-induced cytopathic effects will greatly aid in discovery design new therapeutics to treat COVID-19. Chloroquine hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular including alkalizing lysosomes blocking autophagy well exhibiting dose-limiting toxicities patients. Therefore, we evaluated additional lysosomotropic compounds identify an...
The global impact of SARS-CoV-2 highlights the need for treatments beyond vaccination, given limited availability effective medications. While Pfizer introduced Paxlovid, an FDA-approved antiviral targeting main protease (Mpro), this study focuses on designing new antivirals against another protease, papain-like (PLpro), which is crucial viral replication and immune suppression. NCATS/NIH performed a high-throughput screen ∼15,000 molecules from internal molecular library, identifying...
Abstract SARS-CoV-2 is a new type of coronavirus capable rapid transmission and causing severe clinical symptoms; much which has unknown biological etiology. It prompted researchers to rapidly mobilize their efforts towards identifying developing anti-viral therapeutics vaccines. Discovering understanding the virus’ pathways infection, host-protein interactions, cytopathic effects will greatly aid in design treat COVID-19. While it known that chloroquine hydroxychloroquine, extensively...
Computational approaches for drug discovery, such as quantitative structure–activity relationship, rely on structural similarities of small molecules to infer biological activity but are often limited identifying new candidates in the chemical spaces close known ligands. Here we report a activity-based modeling (BABM) approach, which compound profiles established across multiple assays used signatures predict other or against target. This approach was validated by candidate antivirals Zika...
Introduction: Niclosamide (Nc) is an FDA-approved anthelmintic drug that was recently identified in a repurposing screening to possess antiviral activity against SARS-CoV-2. However, due the low solubility and permeability of Nc, its vivo efficacy limited by poor oral absorption. Method: The current study evaluated novel prodrug Nc (PDN; NCATS-SM4705) improving exposure predicted pharmacokinetic profiles PDN across different species. ADME properties were determined humans, hamsters, mice,...
[reaction: see text] An enantioselective total synthesis of (-)-stemonine (1) is reported via a convergent assembly the acyclic precursor 2. Key transformations include Staudinger-aza-Wittig reaction to form central perhydroazepine ring system and an iodine-induced tandem cyclization construct pyrrolidino-butyrolactone framework.
The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin receptor-like kinase 2 (ALK2) but nonselective for highly homologous ALK3 and shows only modest kinome selectivity. Herein, we describe the discovery novel series selective ALK2 inhibitors by replacing quinolinyl with 4-(sulfamoyl)naphthyl, yielding that exhibit not excellent discrimination versus also high In addition, optimized compound 23 demonstrates good ADME in vivo pharmacokinetic properties.
The synthesis of an advanced component leading to (−)-kendomycin is described. synthetic scheme features the application asymmetric conjugate addition methodology for early generation C13−C14 (E)-trisubstituted olefin, providing efficient assembly ansa chain. Condensation reactions probe two strategies attachment aromatic system.
Abstract The recent global pandemic caused by the new coronavirus SARS-CoV-2 presents an urgent need for therapeutic candidates. While importance of traditional in silico approaches such as QSAR efforts unquestionable, these models fundamentally rely on structural similarity to infer biological activity and are thus prone becoming trapped very nearby chemical spaces already known ligands. For novel unprecedented threats COVID-19 much faster efficient paradigms must be devised accelerate...
A series of nonracemic homoallylic alcohols have been prepared by asymmetric allylation using the (R,R)- and (S,S)-1,2-diamino-1,2-diphenylethane bis-sulfonamide controller ligands for in situ formation chiral B-allyl-1,3,2-diazaborolidines. Diastereofacial selectivity is influenced adjacent stereochemistry incorporated into allyl moiety at C-2, addition to expected role auxiliary. Additional asymmetry aldehyde reactant introduces threefold stereodifferentiation. model developed identify...
Abstract For see ChemInform in Full Text.
Abstract For see ChemInform in Full Text.
Understanding the SARS-CoV-2 virus' routes of infection, virus–host–protein interactions, and mechanisms virus-induced cytopathic effects will greatly aid in discovery design new therapeutics to treat COVID-19. Chloroquine hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular including alkalizing lysosomes blocking autophagy well exhibiting dose-limiting toxicities patients. To identify an alternative lysosome-based drug repurposing opportunity we...