Preliminary Evidence That Inhibitors of Thiol-Mediated Uptake May Block Entry of SARS-C0V-2 into Target Cells

The cell membrane is impermeable to viruses: to get inside and infect a cell, viruses use a range of strategies to exploit the cellular and biochemical properties of the membranes. The thiol-mediated uptake of organic molecules similar to alcohols, where oxygen is replaced by a sulphur atom, is one of the entry mechanisms, with its use by human immunodeficiency virus (HIV) demonstrated a few years ago. No effective inhibitor is currently available because of the robustness of the chemical reactions and bonds at work. A research group from the University of Geneva (UNIGE) has identified inhibitors that are up to 5,000 times more effective than the one most often used today. Preliminary tests--published online on November 18, 2020 in Chemical Science, the flagship journal of the Royal Society of Chemistry--demonstrate the blocking of the cellular entry of viruses expressing the SARS-CoV-2 proteins. The article is titled “Inhibitors of Thiol-Mediated Uptake.” The open-access study paves the way for research into new antivirals. Since 2011, the laboratory led by Professor Stefan Matile in UNIGE's Department of Organic Chemistry, member of the two National Centres of Competence in Research (NCCR) “Chemical Biology” and “Molecular Systems Engineering,” has been investigating the way thiols react with other structures containing sulfur: sulfides, molecules where sulfur is combined with another chemical element. “These are very special chemical reactions because they can change state dynamically,” begins Professor Matile. In fact, covalent bonds, based on sharing electrons between two atoms, freely oscillate between sulfur atoms, depending on conditions. Sulfur compounds are present in nature, particularly on the membrane of eukaryotic cells and on the envelope of viruses, on bacteria, and on toxins.
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