Niemann-Pick type C1 (NPC1) receptor is an endosomal membrane protein that regulates intracellular cholesterol traffic. This protein has been shown to play an important role for several viruses. It has been reported that SARS-CoV-2 enters the cell through plasma membrane fusion and/or endosomal entry upon availability of proteases. However, the whole process is not fully understood yet and additional viral/host factors might be required for viral fusion and subsequent viral replication. Here, we report a novel interaction between the SARS-CoV-2 nucleoprotein (N) and the cholesterol transporter NPC1. Furthermore, we have found that some compounds reported to interact with NPC1, carbazole SC816 and sulfides SC198 and SC073, were able to reduce SARS-CoV-2 viral infection with a good selectivity index in human cell infection models. These findings suggest the importance of NPC1 for SARS-CoV-2 viral infection and a new possible potential therapeutic target to fight against COVID-19.
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http://dx.doi.org/10.1016/j.antiviral.2021.105167 | DOI Listing |
Viruses
January 2025
1st Department of Internal Medicine, Laiko General Hospital, 11527 Athens, Greece.
Background: Cognitive function decline is a problem in aging people living with HIV (PLWHIV). COVID-19 infection is associated with neuropsychiatric manifestations that may persist. The aim of our study was to evaluate cognitive function in PLWHIV before and after COVID-19 infection.
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January 2025
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs in low- to middle-income countries during the COVID-19 pandemic combined with increased transmission of drug-resistant mutants worldwide are leading to an increase in INSTI resistance.
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January 2025
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)-, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation.
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January 2025
School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey 64849, Mexico.
Detection and quantification of disease-related biomarkers in wastewater samples, denominated Wastewater-based Surveillance (WBS), has proven a valuable strategy for studying the prevalence of infectious diseases within populations in a time- and resource-efficient manner, as wastewater samples are representative of all cases within the catchment area, whether they are clinically reported or not. However, analysis and interpretation of WBS datasets for decision-making during public health emergencies, such as the COVID-19 pandemic, remains an area of opportunity. In this article, a database obtained from wastewater sampling at wastewater treatment plants (WWTPs) and university campuses in Monterrey and Mexico City between 2021 and 2022 was used to train simple clustering- and regression-based risk assessment models to allow for informed prevention and control measures in high-affluence facilities, even if working with low-dimensionality datasets and a limited number of observations.
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January 2025
Antiguo Hospital Civil de Guadalajara, "Fray Antonio Alcalde", Guadalajara 44280, Mexico.
This study investigates the relationship between SARS-CoV-2 RT-PCR cycle threshold (Ct) values and key COVID-19 transmission and outcome metrics across five years of the pandemic in Jalisco, Mexico. Utilizing a comprehensive time-series analysis, we evaluated weekly median Ct values as proxies for viral load and their temporal associations with positivity rates, reproduction numbers (Rt), hospitalizations, and mortality. Cross-correlation and lagged regression analyses revealed significant lead-lag relationships, with declining Ct values consistently preceding surges in positivity rates and hospitalizations, particularly during the early phases of the pandemic.
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