tetano
Editor, Senior Moderator
Int J Biol Sci
. 2022 Jul 11;18(12):4714-4730.
doi: 10.7150/ijbs.72709. eCollection 2022.
Targeting ACLY efficiently inhibits SARS-CoV-2 replication
Terrence Tsz-Tai Yuen[SUP] 1 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 4 5 6 [/SUP], Bingpeng Yan[SUP] 1 [/SUP], Cynthia Cheuk-Ying Shum[SUP] 1 [/SUP], Yuanchen Liu[SUP] 1 [/SUP], Huiping Shuai[SUP] 1 [/SUP], Yuxin Hou[SUP] 1 [/SUP], Xiner Huang[SUP] 1 [/SUP], Bingjie Hu[SUP] 1 [/SUP], Yue Chai[SUP] 1 [/SUP], Chaemin Yoon[SUP] 1 [/SUP], Tianrenzheng Zhu[SUP] 1 [/SUP], Huan Liu[SUP] 1 [/SUP], Jialu Shi[SUP] 1 [/SUP], Jinjin Zhang[SUP] 1 [/SUP], Jian-Piao Cai[SUP] 1 [/SUP], Anna Jinxia Zhang[SUP] 1 3 [/SUP], Jie Zhou[SUP] 1 3 [/SUP], Feifei Yin[SUP] 6 7 8 [/SUP], Shuofeng Yuan[SUP] 1 2 3 [/SUP], Bao-Zhong Zhang[SUP] 9 [/SUP], Hin Chu[SUP] 1 2 3 [/SUP]
Affiliations
Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.
Keywords: ACLY; COVID-19; Delta; Omicron; SARS-CoV-2; metabolomics.
. 2022 Jul 11;18(12):4714-4730.
doi: 10.7150/ijbs.72709. eCollection 2022.
Targeting ACLY efficiently inhibits SARS-CoV-2 replication
Terrence Tsz-Tai Yuen[SUP] 1 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 4 5 6 [/SUP], Bingpeng Yan[SUP] 1 [/SUP], Cynthia Cheuk-Ying Shum[SUP] 1 [/SUP], Yuanchen Liu[SUP] 1 [/SUP], Huiping Shuai[SUP] 1 [/SUP], Yuxin Hou[SUP] 1 [/SUP], Xiner Huang[SUP] 1 [/SUP], Bingjie Hu[SUP] 1 [/SUP], Yue Chai[SUP] 1 [/SUP], Chaemin Yoon[SUP] 1 [/SUP], Tianrenzheng Zhu[SUP] 1 [/SUP], Huan Liu[SUP] 1 [/SUP], Jialu Shi[SUP] 1 [/SUP], Jinjin Zhang[SUP] 1 [/SUP], Jian-Piao Cai[SUP] 1 [/SUP], Anna Jinxia Zhang[SUP] 1 3 [/SUP], Jie Zhou[SUP] 1 3 [/SUP], Feifei Yin[SUP] 6 7 8 [/SUP], Shuofeng Yuan[SUP] 1 2 3 [/SUP], Bao-Zhong Zhang[SUP] 9 [/SUP], Hin Chu[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 35874959
- PMCID: PMC9305265
- DOI: 10.7150/ijbs.72709
Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.
Keywords: ACLY; COVID-19; Delta; Omicron; SARS-CoV-2; metabolomics.