Publications by authors named "Van Ngoc Thuy La"
The coronavirus main protease (MPro) plays a pivotal role in viral replication and is the target of several antivirals against SARS-CoV-2. In some species, CRCs of MPro enzymatic activity can exhibit biphasic behavior in which low ligand concentrations activate the enzyme whereas higher ones inhibit it. While this behavior has been attributed to ligand-induced dimerization, quantitative enzyme kinetics models have not been fit to it.
View Article and Find Full Text PDFOpen science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors.
Science
November 2023
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.
Concentration-response curves, in which the effect of varying the concentration on the response of an assay is measured, are widely used to evaluate biological effects of chemical compounds. While National Center for Advancing Translational Sciences guidelines specify that readouts should be normalized by the controls, recommended statistical analyses do not explicitly fit to the control data. Here, we introduce a nonlinear regression procedure based on maximum likelihood estimation that determines parameters for the classical Hill equation by fitting the model to both the curve and the control data.
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