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http://dx.doi.org/10.20411/pai.v8i1.624 | DOI Listing |
Toxicol Sci
December 2024
Ronald Swanstrom, Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
J Med Chem
December 2024
Aligos Belgium BV, Gaston Geenslaan 1, 3001 Leuven, Belgium.
Chronic hepatitis B (CHB) represents a significant unmet medical need with few options beyond lifelong treatment with nucleoside analogues, which rarely leads to a functional cure. Novel agents that reduce levels of HBV DNA, RNA and other viral antigens could lead to better treatment outcomes. The capsid assembly modulator (CAM) class of compounds represents an important modality for chronic suppression and to improve functional cure rates, either alone or in combination.
View Article and Find Full Text PDFMolecules
October 2024
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, 280 Calhoun St, Charleston, SC 29425, USA.
mBio
November 2024
Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
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 viral breakthrough assays identified the HIV-1 variant that confers substantial resistance to this inhibitor.
View Article and Find Full Text PDFVirology
December 2024
Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, 30322, USA; Center for ViroScience and Cure, Children's Healthcare of Atlanta, GA, 30322, USA. Electronic address:
We biochemically simulated the mutation synthesis process of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex (nsp7/nsp8/nsp12) involving two sequential mechanistic steps that occur during genomic replication: misinsertion (incorporation of incorrect nucleotides) and mismatch extension. Then, we also simulated mismatch repair process catalyzed by the viral nsp10/nsp14 ExoN complex. In these mechanistic simulations, while SARS-CoV-2 RdRp displays efficient mutation synthesis capability, the viral ExoN complex was able to effectively repair the mismatch primers generated during the mutation synthesis.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!