An essential protein of the SARS-CoV-2 virus, the envelope protein E, forms a homopentameric cation channel that is important for virus pathogenicity. Here we report a 2.1-Å structure and the drug-binding site of E's transmembrane domain (ETM), determined using solid-state NMR spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow pore. The protein deviates from the ideal α-helical geometry due to three phenylalanine residues, which stack within each helix and between helices. Together with valine and leucine interdigitation, these cause a dehydrated pore compared with the viroporins of influenza viruses and HIV. Hexamethylene amiloride binds the polar amino-terminal lumen, whereas acidic pH affects the carboxy-terminal conformation. Thus, the N- and C-terminal halves of this bipartite channel may interact with other viral and host proteins semi-independently. The structure sets the stage for designing E inhibitors as antiviral drugs.
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http://dx.doi.org/10.1038/s41594-020-00536-8 | DOI Listing |
Sci Rep
January 2025
Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains a major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated the potential repurposing of domperidone, an antiemetic and gastrokinetic agent, to control DENV infection. Domperidone was identified by pharmacophore-based virtual screening as a small molecule that can bind to both the viral envelope (E) and the nonstructural protein 1 (NS1) of DENV.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France. Electronic address:
Protein mycoloylation is a newly characterized post-translational modification (PTM) specifically found in Corynebacteriales, an order of bacteria that includes numerous human pathogens. Their envelope is composed of a unique outer membrane, the so-called mycomembrane made of very-long chain fatty acids, named mycolic acids. Recently, some mycomembrane proteins including PorA have been unambiguously shown to be covalently modified with mycolic acids in the model organism Corynebacterium glutamicum by a mechanism that relies on the mycoloyltransferase MytC.
View Article and Find Full Text PDFJ Virol
January 2025
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
The evolution of SARS-CoV-2 pathogenicity has been a major focus of attention. However, the determinants of pathogenicity are still unclear. Various hypotheses have attempted to elucidate the mechanisms underlying the evolution of viral pathogenicity, but a definitive conclusion has yet to be reached.
View Article and Find Full Text PDFJ Gastrointest Cancer
January 2025
Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China.
Purpose: Liquid biopsy technology has received widespread attention in the early diagnosis of cholangiocarcinoma (CCA).
Methods: We collected bile samples from 48 patients with CCA and 48 patients with gallstones at Shandong Provincial third Hospital. We quantified bile circulating free DNA (cfDNA) of syncytin-1 and SLC7A11, calculated the correlation between syncytin-1 and SLC7A11 expression and clinical parameters by Spearman rank correlation, plotted Receiver Operating Characteristic (ROC) curves, and compared the Area Under Curve (AUC) values to explored early diagnostic utility in patients.
J Bacteriol
January 2025
Department of Microbiology, Howard Taylor Ricketts Laboratory, The University of Chicago, Chicago, Illinois, USA.
Unlabelled: Bacteria transport proteins across the plasma membrane to assemble their envelope, acquire nutrients, and establish appropriate interactions with their environment. The majority of these proteins are synthesized as precursors with a cleavable N-terminal signal sequence for recognition by the Sec machinery. In , a small subset of secreted precursors carries a YSIRK/GXXS motif.
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