Targeting ACLY efficiently inhibits SARS-CoV-2 replication

被引：7

作者：

Yuen, Terrence Tsz-Tai ^{[1
,2
]}

Chan, Jasper Fuk-Woo ^{[1
,2
,3
,4
,5
,6
,7
,8
]}

Yan, Bingpeng ^{[1
,2
]}

Shum, Cynthia Cheuk-Ying ^{[1
,2
]}

Liu, Yuanchen ^{[1
,2
]}

Shuai, Huiping ^{[1
,2
]}

Hou, Yuxin ^{[1
,2
]}

Huang, Xiner ^{[1
,2
]}

Hu, Bingjie ^{[1
,2
]}

Chai, Yue ^{[1
,2
]}

Yoon, Chaemin ^{[1
,2
]}

Zhu, Tianrenzheng ^{[1
,2
]}

Liu, Huan ^{[1
,2
]}

Shi, Jialu ^{[1
,2
]}

Zhang, Jinjin ^{[1
,2
]}

Cai, Jian-Piao ^{[1
,2
]}

Zhang, Anna Jinxia ^{[1
,2
,4
]}

Zhou, Jie ^{[1
,2
,4
]}

Yin, Feifei ^{[7
,8
,9
,10
]}

Yuan, Shuofeng ^{[1
,2
,3
,4
]}

Zhang, Bao-Zhong ^{[11
]}

Chu, Hin ^{[1
,2
,3
,4
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Dept Microbiol,Pokfulam, Hong Kong, Peoples R China

[2] Univ Hong Kong, Li Ka Shing Fac Med, Carol Yu Ctr Infect, Sch Clin Med,Pokfulam, Hong Kong, Peoples R China

[3] Univ Hong Kong, Dept Clin Microbiol & Infect Control, Shenzhen Hosp, Shenzhen, Guangdong, Peoples R China

[4] Hong Kong Sci & Technol Pk, Ctr Virol Vaccinol & Therapeut, Hong Kong, Peoples R China

[5] Queen Mary Hosp, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China

[6] Guangzhou Lab, Guangzhou, Guangdong, Peoples R China

[7] Hainan Med Univ, Hainan Med Univ Univ Hong Kong Joint Lab Trop Inf, Academician Workstn Hainan Prov, Haikou, Hainan, Peoples R China

[8] Univ Hong Kong, Pokfulam, Hong Kong, Peoples R China

[9] Hainan Med Univ, Key Lab Trop Translat Med, Minist Educ, Haikou, Hainan, Peoples R China

[10] Hainan Med Univ, Dept Pathogen Biol, Haikou, Hainan, Peoples R China

[11] Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, CAS Key Lab Quantitat Engn Biol, Shenzhen, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2022年 / 18卷 / 12期

基金：

中国国家自然科学基金;

关键词：

COVID-19; metabolomics; ACLY; SARS-CoV-2; Delta; Omicron; RESPIRATORY SYNDROME CORONAVIRUS; VIRUS; CELLS;

D O I：

10.7150/ijbs.72709

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4714 / 4730

页数：17

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