The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe COVID-19 patients, due to a lack of understanding of the SARS-CoV-2 life cycle. Lysosomes, which act as "garbage disposals" for nearly all types of eukaryotic cells, were shown in numerous studies to support SARS-CoV-2 replication. Lysosome-associated pathways are required for virus entry and exit during replication. In this review, we summarize experimental evidence demonstrating a correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents.
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http://dx.doi.org/10.3390/ijms23116188 | DOI Listing |
Infect Drug Resist
January 2025
Department of Public Health, School of Allied Health Sciences, Kampala International University, Western Campus, Uganda.
Introduction: Coronavirus Disease 19 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and Human Immunodeficiency Virus (HIV) are significant 21st-century pandemics with distinct virological and clinical characteristics. COVID-19 primarily presents as an acute respiratory illness, while HIV leads to chronic immune suppression. Understanding their differences can enhance public health strategies and treatment approaches.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Molecular Microbiology and Structural Biochemistry, MMSB-IBCP, CNRS UMR 5086 , Université Claude Bernard Lyon 1, F-69367 Lyon, France.
The nonsense-mediated mRNA decay (NMD) pathway triggers the degradation of defective mRNAs and governs the expression of mRNAs with specific characteristics. Current understanding indicates that NMD is often significantly suppressed during viral infections to protect the viral genome. In numerous viruses, this inhibition is achieved through direct or indirect interference with the RNA helicase UPF1, thereby promoting viral replication and enhancing pathogenesis.
View Article and Find Full Text PDFPNAS Nexus
January 2025
Department of Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.
View Article and Find Full Text PDFJ Drug Deliv Sci Technol
February 2025
Department of Chemical Engineering, University of Rhode Island, Kingston, RI 02881 USA.
Macrophages are an integral part of the innate immune system and act as a first line of defense to pathogens; however, macrophages can be reservoirs for pathogens to hide and replicate. Tuberculosis, influenza virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are common diseases whose pathogens are uptaken into macrophages. Current treatments for diseases such as these are limited by the therapeutic delivery method, which typically involves systemic delivery in large, frequent doses.
View Article and Find Full Text PDFMolnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication. Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes.
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