PT  - JOURNAL ARTICLE
AU  - Minhyoung Lee
AU  - Michael Sugiyama
AU  - Katrina Mekhail
AU  - Elyse Latreille
AU  - Negar Khosraviani
AU  - Kuiru Wei
AU  - Warren L. Lee
AU  - Costin Antonescu
AU  - Gregory D. Fairn
TI  - Fatty Acid Synthase inhibition prevents palmitoylation of SARS-CoV2 Spike Protein and improves survival of mice infected with murine hepatitis virus
AID  - 10.1101/2020.12.20.423603
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.20.423603
4099  - http://biorxiv.org/content/early/2020/12/21/2020.12.20.423603.short
4100  - http://biorxiv.org/content/early/2020/12/21/2020.12.20.423603.full
AB  - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the causative agent of COVID19 that has infected >76M people and caused >1.68M deaths. The SARS-CoV2 Spike glycoprotein is responsible for the attachment and infection of target cells. The viral Spike protein serves the basis for many putative therapeutic countermeasures including vaccines, blocking and neutralizing antibodies, and decoy receptors. Here we investigated the cytosolic domain of Spike and its interaction with the protein palmitoyltransferase ZDHHC5. The Spike protein is palmitoylated on multiple juxtamembrane cysteine residues conserved among coronavirus. Increased abundance of ZDHHC5 resulted in hyper-palmitoylation, while silencing of ZDHHC5 reduced the ability of the human CoV 229E to form viral plaques in cell monolayers. Inhibition of fatty acid synthase using the pharmacological inhibitor TVB-3166 eliminated palmitoylation of SARS-CoV2 Spike. Additionally, TVB-3166 attenuated plaque formation and promoted the survival of mice from a lethal murine CoV infection. Thus, inhibition of the Spike protein palmitoylation has the potential to treat SARS-CoV-2 and other CoV infections.Competing Interest StatementThe authors have declared no competing interest.