The novel coronavirus (SARS-CoV-2) affects primarily the respiratory tract, and if left unchecked can cause a spectrum of pathological manifestations such as pneumonia, acute respiratory distress syndrome, myocardial injury, thromboembolism, and acute kidney injury. Medication strategies have involved minimizing the spread of the virus through antiviral medications (monoclonal antibodies or nucleotide reverse transcriptase inhibitors). Here, we develop a mathematical model that simulates viral dynamics in an untreated individual, and the evaluate the impact that a monoclonal antibody can have on slowing viral replication. Drug pharmacokinetics (PK) was informed by a typical two-compartment PK model with parameters typical of a monoclonal antibody, with a third compartment for the lung included as the drug site of action. The viral dynamics were captured using a simplified model describing uninfected target cells, infected target cells, and viral load in the body. The mechanism of action of the simulated antiviral is based on binding to the virus, thereby preventing it from infecting healthy cells. The model is used to project dosages needed to prevent severe disease under a variety of simulated conditions and subject to realistic constraints. The proposed model can capture a variety of scenarios of longitudinal viral dynamics and assess the impact of antiviral therapy on disease severity and duration. The described approach can be easily adapted to rapidly assess the dosages needed to affect duration and outcome of other viral infections and can serve as part of a fast and efficient scientific and modeling response strategy in the future as needed.
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http://dx.doi.org/10.1016/j.ifacol.2023.01.038 | DOI Listing |
Chem Biodivers
January 2025
Universidad Nacional del Litoral Facultad de Bioquimica y Ciencias Biologicas, Química Orgánica, Ciudad Universitaria. Paraje el Pozo S/N, Argentina, 3000, Santa Fe, ARGENTINA.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has highlighted the urgent need for novel therapeutic agents targeting viral enzymes such as the main protease (Mpro), which plays a crucial role in viral replication. In this study, we investigate the inhibitory potential of 23 peptides isolated from the skin of amphibians belonging to the Hylidae and Leptodactylidae families against SARS-CoV-2 Mpro. Five peptides demonstrated significant inhibition using a colorimetric Mpro inhibition assay, with IC50 values ranging from 41 to 203 µM.
View Article and Find Full Text PDFPLoS Pathog
January 2025
The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
HIV infection implicates a spectrum of tissues in the human body starting with viral transmission in the anogenital tract and subsequently persisting in lymphoid tissues and brain. Though studies using isolated cells have contributed significantly towards our understanding of HIV infection, the tissue microenvironment is characterised by a complex interplay of a range of factors, all of which can influence the course of infection but are otherwise missed in ex vivo studies. To address this knowledge gap, it is necessary to investigate the dynamics of infection and the host immune response in situ using imaging-based approaches.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
SARS-CoV-2 continues to transmit and evolve in humans and animals. White-tailed deer (Odocoileus virginianus) have been previously identified as a zoonotic reservoir for SARS-CoV-2 with high rates of infection and probable spillback into humans. Here we report sampling 1,127 white-tailed deer (WTD) in Pennsylvania, and a genomic analysis of viral dynamics spanning 1,017 days between April 2021 and January 2024.
View Article and Find Full Text PDFPLoS Biol
January 2025
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
The unique architecture of the liver consists of hepatic lobules, dividing the hepatic features of metabolism into 2 distinct zones, namely the pericentral and periportal zones, the spatial characteristics of which are broadly defined as metabolic zonation. R-spondin3 (Rspo3), a bioactive protein promoting the Wnt signaling pathway, regulates metabolic features especially around hepatic central veins. However, the functional impact of hepatic metabolic zonation, regulated by the Rspo3/Wnt signaling pathway, on whole-body metabolism homeostasis remains poorly understood.
View Article and Find Full Text PDFPLoS One
January 2025
Neuroscience Center, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia.
Hepatitis C Virus (HCV) is a blood borne pathogen that affects around 200 million individuals worldwide. Immunizations against the Hepatitis C Virus are intended to enhance T-cell responses and have been identified as a crucial component of successful antiviral therapy. Nevertheless, attempts to mediate clinically relevant anti-HCV activity in people have mainly failed, despite the vaccines present satisfactory progress.
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