SARS-CoV-2 ORF3a accessory protein is a water-permeable channel that induces lysosome swelling.

ABSTRACT: ORF3a, the most abundantly expressed accessory protein of SARS-CoV-2, plays an essential role in virus egress by inactivating lysosomes through their deacidification. However, the mechanism underlying this process remains unclear. While seminal studies suggested ORF3a being a cation-selective channel (i.e., viroporin), recent works disproved this conclusion. To unravel the potential function of ORF3a, here we employed a multidisciplinary approach including patch-clamp electrophysiology, videoimaging, molecular dynamics (MD) simulations, and electron microscopy. Preliminary structural analyses and patch-clamp recordings in HEK293 cells rule out ORF3a functioning as either viroporin or proton (H⁺) channel. Conversely, videoimaging experiments demonstrate that ORF3a mediates the tr

SUBMITTER: Michelucci A 

PROVIDER: S-EPMC11794868 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature