Palmitoylation of SARS-CoV-2 Envelope protein is central to virus particle formation

• DOI: 10.1128/jvi.01072-24
• Publication Date: 2024-09-17T17:00:36Z
• Authors: Zhaohuan Wang; Manman Qiu; Yue Ji; Keli Chai; Chenxi Liu; Fengwen Xu; Fei Guo; Juan Tan; Ruikang Liu; Wentao Qiao
• Keywords: Palmitoylation; Coronavirus

ABSTRACT The Envelope (E) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an integral structural in the virus particles. However, its role assembly virions and underlying molecular mechanisms are yet to be elucidated, including whether function E regulated by post-translational modifications. In present study, we report that SARS-CoV-2 palmitoylated at C40, C43, C44 palmitoyltransferases zDHHC3, 6, 12, 15, 20. Mutating these three cysteines serines (C40/43/44S) reduced stability protein, decreased interaction with proteins Spike, Membrane, Nucleocapsid, thereby inhibited production virus-like particles (VLPs) VLP-mediated luciferase transcriptional delivery. Specifically, C40/43/44S mutation density VLPs. Collectively, results demonstrate palmitoylation vital for IMPORTANCE this systematically examined biochemistry demonstrated required particle (VLP) maintaining normal density. These suggest central proper morphogenesis VLPs densities viral infectivity. This study presents a significant advancement understanding how assembling supports palmitoyl acyltransferases can potential therapeutic targets development inhibitors.