biostudies-literatureJalily PHNatural Sciences and Engineering Research Council of CanadaHeart and Stroke FoundationHeart and Stroke Foundation of CanadaNatural Sciences and Engineering Research CouncilCanadian Institutes of Health ResearchCIHR10647https://www.ebi.ac.uk/biostudies/studies/S-EPMC9503309biostudies-literatureUnknown23(18)The coronavirus E proteins are small membrane proteins found in the virus envelope of alpha and beta coronaviruses that have a high degree of overlap in their biochemical and functional properties despite minor sequence variations. The SARS-CoV-2 E is a 75-amino acid transmembrane protein capable of acting as an ion channel when assembled in a pentameric fashion. Various studies have found that hexamethylene amiloride (HMA) can inhibit the ion channel activity of the E protein in bilayers and also inhibit viral replication in cultured cells. Here, we use the available structural data in conjunction with homology modelling to build a comprehensive model of the E protein to assess potential binding sites and molecular interactions of HMA derivatives. Furthermore, we employed an iterative cycInternational journal of molecular sciencesIn Silico Evaluation of Hexamethylene Amiloride Derivatives as Potential Luminal Inhibitors of SARS-CoV-2 E Protein.PMC9503309PJT-156181RGPIN-2016-05422G-17-0018392PJT-175024G-21-003156600-00Jalily PHFedida DJalily Hasani HfalseIn Silico Evaluation of Hexamethylene Amiloride Derivatives as Potential Luminal Inhibitors of SARS-CoV-2 E Protein.The coronavirus E proteins are small membrane proteins found in the virus envelope of alpha and beta coronaviruses that have a high degree of overlap in their biochemical and functional properties despite minor sequence variations. The SARS-CoV-2 E is a 75-amino acid transmembrane protein capable of acting as an ion channel when assembled in a pentameric fashion. Various studies have found that hexamethylene amiloride (HMA) can inhibit the ion channel activity of the E protein in bilayers and also inhibit viral replication in cultured cells. Here, we use the available structural data in conjunction with homology modelling to build a comprehensive model of the E protein to assess potential binding sites and molecular interactions of HMA derivatives. Furthermore, we employed an iterative cyc2022-01-01T00:00:00Z2022 Sep2026-04-08T11:50:05.526Z2025-02-19T00:44:03.92ZS-EPMC95033093614255610.3390/ijms231810647