| Autor: |
Shuofeng Yuan, Bingpeng Yan, Jianli Cao, Zi-Wei Ye, Ronghui Liang, Kaiming Tang, Cuiting Luo, Jianpiao Cai, Hin Chu, Tom Wai-Hing Chung, Kelvin Kai-Wang To, Ivan Fan-Ngai Hung, Dong-Yan Jin, Jasper Fuk-Woo Chan, Kwok-Yung Yuen |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cell Discovery, Vol 7, Iss 1, Pp 1-13 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2056-5968 |
| DOI: |
10.1038/s41421-021-00338-2 |
| Popis: |
Abstract Coronavirus Disease 2019 (COVID-19) is predominantly a respiratory tract infection that significantly rewires the host metabolism. Here, we monitored a cohort of COVID-19 patients’ plasma lipidome over the disease course and identified triacylglycerol (TG) as the dominant lipid class present in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced metabolic dysregulation. In particular, we pinpointed the lipid droplet (LD)-formation enzyme diacylglycerol acyltransferase (DGAT) and the LD stabilizer adipocyte differentiation-related protein (ADRP) to be essential host factors for SARS-CoV-2 replication. Mechanistically, viral nucleo capsid protein drives DGAT1/2 gene expression to facilitate LD formation and associates with ADRP on the LD surface to complete the viral replication cycle. DGAT gene depletion reduces SARS-CoV-2 protein synthesis without compromising viral genome replication/transcription. Importantly, a cheap and orally available DGAT inhibitor, xanthohumol, was found to suppress SARS-CoV-2 replication and the associated pulmonary inflammation in a hamster model. Our findings not only uncovered the mechanistic role of SARS-CoV-2 nucleocapsid protein to exploit LDs-oriented network for heightened metabolic demand, but also the potential to target the LDs-synthetase DGAT and LDs-stabilizer ADRP for COVID-19 treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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