Hexamethylene amiloride binds the SARS-CoV-2 envelope protein at the protein-lipid interface.

ABSTRACT: The SARS-CoV-2 envelope (E) protein forms a five-helix bundle in lipid bilayers whose cation-conducting activity is associated with the inflammatory response and respiratory distress symptoms of COVID-19. E channel activity is inhibited by the drug 5-(N,N-hexamethylene) amiloride (HMA). However, the binding site of HMA in E has not been determined. Here we use solid-state NMR to measure distances between HMA and the E transmembrane domain (ETM) in lipid bilayers. ¹³ C, ¹⁵ N-labeled HMA is combined with fluorinated or ¹³ C-labeled ETM. Conversely, fluorinated HMA is combined with ¹³ C, ¹⁵ N-labeled ETM. These orthogonal isotopic labeling patterns allow us to conduct dipolar recoupling NMR experiments to determine the HMA binding stoichi

SUBMITTER: Somberg NH 

PROVIDER: S-EPMC10503410 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature