Decoding Allosteric Effects of Missense Variations in Drug Metabolism: Afrocentric CYP3A4 Alleles Explored

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169160 - 169160

Published: April 1, 2025

Language: Английский

Transfer Learning Towards Predicting Viral Missense Mutations: A Case Study on SARS-CoV-2

Computational and Structural Biotechnology Journal, Journal Year: 2025, Volume and Issue: 27, P. 1686 - 1692

Published: Jan. 1, 2025

Understanding viral evolution and predicting future mutations are crucial for overcoming drug resistance developing long-lasting treatments. Previously, we established machine learning (ML) models using dynamic residue network (DRN) metric data leveraging a vast amount of existing mutation from the SARS-CoV-2 main protease (Mpro). Here, sought to assess generalizability robustness current across other proteins. To achieve this, first time, employed transfer (TL) approach, allowing us determine extent which Mpro trained could be applied The TL results were highly promising, with artificial neural (ANN) random forest (RF) correlation coefficients closely matching those NSP10, NSP16, PLpro. ANN |R| value was 0.564, while PLpro had values 0.533, 0.527, 0.464, respectively. Similarly, RF 0.673, compared 0.457, 0.460, 0.437 PLpro, Interestingly, did not observe strong spike (S) protein monomer its domains. low p-values that associated show linear correlations between predicted actual frequencies statistically significant. This indicates may generalize well structurally related proteins DRN-derived ML model Mpro. Overall, aim develop universal missense in proteins, this study lays foundation goal.

Language: Английский

SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored. Our study investigates persistent symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as "Long COVID", which has significantly affected millions globally. We meticulously describe outcomes five patients, encompassing range of severe conditions such sudden cardiac death during exercise, coronary atherosclerotic heart disease, palpitation, chest tightness, and acute myocarditis. All patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy histochemical staining, identified inflammatory cell infiltration tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations presence myofilament degradation within cardiomyocytes these patients. These findings mirrored SARS-CoV-2-infected mice, suggesting potential underlying cellular mechanism effects associated COVID. demonstrate profound impact SARS-CoV-2 on integrity, shedding light implications

Language: Английский