4.7 Article

Palmitoylation of SARS-CoV-2 S protein is critical for S-mediated syncytia formation and virus entry

Journal

JOURNAL OF MEDICAL VIROLOGY
Volume 94, Issue 1, Pages 342-348

Publisher

WILEY
DOI: 10.1002/jmv.27339

Keywords

palmitoylation; SARS-CoV-2; spike; syncytia; ZDHHC

Categories

Funding

  1. National Natural Science Foundation of China
  2. Shandong Provincial Natural Science Foundation
  3. Academic Promotion Programme of Shandong First Medical University

Ask authors/readers for more resources

This study characterized the palmitoylation of SARS-CoV-2 S protein and highlighted its critical role in syncytia formation and virus entry. Overexpression of specific ZDHHCs promoted the palmitoylation of S, demonstrating their association with the viral protein.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The S protein is the key viral protein for associating with ACE2, the receptor for SARS-CoV-2. There are many kinds of posttranslational modifications in S protein. However, the detailed mechanism of palmitoylation of SARS-CoV-2 S remains to be elucidated. In our current study, we characterized the palmitoylation of SARS-CoV-2 S. Both the C15 and cytoplasmic tail of SARS-CoV-2 S were palmitoylated. Fatty acid synthase inhibitor C75 and zinc finger DHHC domain-containing palmitoyltransferase (ZDHHC) inhibitor 2-BP reduced the palmitoylation of S. Interestingly, palmitoylation of SARS-CoV-2 S was not required for plasma membrane targeting of S but was critical for S-mediated syncytia formation and SARS-CoV-2 pseudovirus particle entry. Overexpression of ZDHHC2, ZDHHC3, ZDHHC4, ZDHHC5, ZDHHC8, ZDHHC9, ZDHHC11, ZDHHC14, ZDHHC16, ZDHHC19, and ZDHHC20 promoted the palmitoylation of S. Furthermore, those ZDHHCs were identified to associate with SARS-CoV-2 S. Our study not only reveals the mechanism of S palmitoylation but also will shed important light into the role of S palmitoylation in syncytia formation and virus entry.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available