Publications by authors named "Jasmin C Aschenbrenner"
Article Synopsis
- - Chikungunya virus (CHIKV) causes severe symptoms like fever, rash, and joint pain, with millions infected, primarily in low and middle-income regions, due to its mosquito carriers spreading into new areas.
- - The virus has a macrodomain in its genome that interferes with the immune response, making it essential for viral replication, which positions it as a potential target for antiviral drug development.
- - A high-throughput crystallographic fragment screen identified 109 fragments that bind to the CHIKV nsP3 macrodomain, leading to the design of three fragments aimed at trapping the active sites, and this data is publicly available for future research.
A strategy for pandemic preparedness is the development of antivirals against a wide set of viral targets with complementary mechanisms of action. SARS-CoV-2 nsp3-mac1 is a viral macrodomain with ADP-ribosylhydrolase activity, which counteracts host immune response. Targeting the virus' immunomodulatory functionality offers a differentiated strategy to inhibit SARS-CoV-2 compared to approved therapeutics, which target viral replication directly.
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- - The 2A protease of enterovirus species, responsible for critical steps in viral replication, is a key target for combating pediatric hand-foot-and-mouth disease and preparing for potential outbreaks.
- - Inhibiting the 2A protease can disrupt the folding and assembly of viral capsid proteins, preventing the production of mature viral particles and presenting a strategy for antiviral treatment.
- - A crystallographic fragment screening campaign successfully identified 75 compounds that bind to the 2A protease, with 38 unique ones targeting the active site, paving the way for the creation of broad-spectrum anti-enteroviral drugs.
Article Synopsis
- - Zika virus (ZIKV) infections are linked to serious health issues like microcephaly in newborns and Guillain-Barre syndrome in adults, with no current vaccines or antiviral treatments available.
- - The NS3 protease and its co-factor NS2B play a crucial role in processing viral proteins, making them a key target for drug development.
- - A successful crystallographic study identified 48 compounds that bind to the NS2B-NS3 protease, along with 6 additional fragments targeting a possible allosteric site, paving the way for new inhibitors to be developed.
Article Synopsis
- * The NS3 helicase protein of ZIKV is a key target for drug development due to its role in viral replication, but challenges exist due to inadequate structural data for designing specific inhibitors.
- * High-throughput crystallographic fragment screening identified 46 fragments that bind to NS3, providing valuable 3D structures that can help design new antiviral drugs to combat ZIKV and other flaviviruses.
Article Synopsis
- - The COVID Moonshot was a collaborative, open-science effort focused on finding a new drug to inhibit the SARS-CoV-2 main protease, which is crucial for the virus's survival.
- - Researchers developed a novel noncovalent, nonpeptidic inhibitor that stands out from existing drugs targeting the same protease, employing advanced techniques like machine learning and high-throughput structural biology.
- - Over 18,000 compound designs, 490 ligand-bound x-ray structures, and extensive assay data were generated and shared openly, creating a comprehensive and accessible knowledge base for future drug discovery efforts against coronaviruses.
Cytochrome P450 monooxygenases (CYP450s) are abundant in eukaryotes, specifically in plants and fungi where they play important roles in the synthesis and degradation of secondary metabolites. In eukaryotes, the best studied "self-sufficient" CYP450s, with a fused redox partner, belong to the CYP505 family. Members of the CYP505 family are generally considered sub-terminal fatty acid hydroxylases.
View Article and Find Full Text PDFBiocatalysts are receiving increased attention in the field of selective oxyfunctionalization of C-H bonds, with cytochrome P450 monooxygenases (CYP450s), and the related peroxygenases, leading the field. Here we report on the substrate promiscuity of CYP505A30, previously characterized as a fatty acid hydroxylase. In addition to its regioselective oxyfunctionalization of saturated fatty acids (ω-1 - ω-3 hydroxylation), primary fatty alcohols are also accepted with similar regioselectivities.
View Article and Find Full Text PDFToxoplasmosis is a parasitic disease caused by infection with Toxoplasma gondii that currently has few therapeutic options. The M1 aminopeptidase enzymes have been shown to be attractive targets for anti-parasitic agents and/or vaccine candidates, suggesting potential to re-purpose inhibitors between parasite M1 aminopeptidase targets. The M1 aminopeptidase TgAPN2 has been suggested to be a potential new drug target for toxoplasmosis.
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