The Distribution of Angiotensin-Converting Enzyme 2 (ACE2) and the Intervention Strategies Targeting the Binding Process of SARS-CoV-2 and ACE2
ZHANG Qiao1,2, LIU Xue-ling1,2, LIN Mei-hua1,2, LIU Jian1,2, ZHAO Qing-wei1,2*
1. First Affiliated Hospital, College of Medical, Zhejiang University, Hangzhou 310003, China; 2. Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou 310003, China
Abstract：SARS-CoV-2, which is similar to SARS-CoV, can bind to human cell surface receptor ACE2 through its S-protein, sequentially infecting human cells such as respiratory epithelial cells or corneal and conjunctival tissues, thereby invading the human body. Recent studies have shown that organs with high expression levels of ACE2 protein, such as kidneys and lungs, are more vulnerable to virus damage. Therefore, lots of efforts have been devoted to the development of drugs targeting the combination of SARS-CoV-2 and ACE2. This paper reviewed the most recently published literatures that related to ACE2 and coronavirus infection, with an emphasis on ACE2, especially its distribution in vivo and organ damages of the patients with SARS-CoV-2 infection, as well as recent progress of drug development targeting the binding process of SARS-CoV-2 and ACE2. This paper aimed to shed some light on clinically fight against SARS-CoV-2 infection.
张乔, 刘雪玲, 林美花, 刘健, 赵青威. 血管紧张素转化酶2的体内分布及针对新型冠状病毒与其结合过程的干预策略[J]. 中国药学杂志, 2020, 55(9): 665-670.
ZHANG Qiao, LIU Xue-ling, LIN Mei-hua, LIU Jian, ZHAO Qing-wei. The Distribution of Angiotensin-Converting Enzyme 2 (ACE2) and the Intervention Strategies Targeting the Binding Process of SARS-CoV-2 and ACE2. Chinese Pharmaceutical Journal, 2020, 55(9): 665-670.
HOFFMANN M. The novel coronavirus 2019 (2019-NcOv) uses the ARS coronavirus receptor ACE2 and the cellular for entry into protease TMPRSS2 target cells[DB/OL]. BioRxiv. [2020-03-11]. https://doi.org/10.1101/2020.01.31.929042.
[2]
TIAN X L, LI C, HUANG A L, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody[J]. Emerg Microbes Infect, 2020,9(1):382-385.
[3]
WRAPP D, WANG N S, CORBETT K S, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation[J]. Science, 2020, 367(6483):1260-1263.
[4]
XU X T. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission[J]. Sci China Life Sci, 2020, 63(3):457-460.
[5]
LI X, DUAN G Y, ZHANG W, et al. A furin cleavage site was discovered in the S protein of the 2019 novel coronavirus[J]. Chin J Bioinform(生物信息学),2020,18(2):1-4.
[6]
CAI G S. Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov [DB/OL]. BioRxiv. [2020-03-11]. https://www.preprints.org/manuscript/202002.0051/v3.
[7]
ZHAO Y. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov [DB/OL]. BioRxiv. [2020-03-11]. https://doi.org/10.1101/2020.02.11.20022228.
[8]
ZHANG Y, TANG D Z, SHU B, et al. Evaluation and analysis on the SARS-CoV-2-induced injuries in multiple organs and the intervention of traditional Chinese medicine based on renin-angiotensin system[J]. World Sci Technol Mod Tradit Chin Med(世界科学技术—中医药现代化),2020,22(2):1-7.
[9]
WU Y T. Compensation of ACE2 Function for Possible Clinical Management of 2019-nCoV-Induced Acute Lung Injury[DB/OL]. Virol Sin.[2020-02-07]. https://link.springer.com/article/10.1007/s12250-020-00205-6.
[10]
HUANG C L, WANG Y M, LI X W, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. Lancet, 2020, 395(10233):497-506.
[11]
HAMMING I, TIMENS W, BULTHUIS M L C, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis[J]. J Pathol, 2004, 203(2):631-637.
[12]
ZOU X, CHEN K, ZOU J W, et al. The single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan 2019-nCoV infection[DB/OL]. Front Med. [2020-03-12]. https://link.springer.com/article/10.1007%2Fs11684-020-0754-0.
[13]
LI Z. Caution on Kidney Dysfunctions of 2019-nCoV Patients [DB/OL]. BioRxiv. [2020-03-11]. https://doi.org/10.1101/2020.02.08.20021212.
[14]
ZHANG H. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes [DB/OL]. BioRxiv. [2020-03-11]. https://doi.org/10.1101/2020.01.30.927806.
[15]
JIA H P. Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease[J]. Shock, 2016, 46(3):239-248.
[16]
IMAI Y, KUBA K, RAO S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure[J]. Nature, 2005, 436(7047):112-116.
[17]
ZHANG M, LI C, Novel coronavirus pneumonia and cardiovascular disease[J]. Med J Chin PAPF(武警医学),2020, 2(31):93-96.
[18]
LIU Y X, YANG Y, ZHANG C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury[J]. Sci China Life Sci, 2020, 63(3):364-374.
[19]
LI G D, CLERCQ E D. Therapeutic options for the 2019 novel coronavirus (2019-nCoV)[J]. Nat Rev Drug Discov, 2020, 19(3):149-150.
[20]
FAN C B. ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection [DB/OL]. MedRxiv. [2020-03-11]. https://doi.org/10.1101/2020.02.12.20022418.
[21]
CHAI X Q. Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection [DB/OL]. BioRxiv. [2020-03-11]. https://doi.org/10.1101/2020.02.03.931766.
[22]
MORSE J S, LALONDE T, XU S Q, et al. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV[J]. Chem Bio Chem, 2020, 21(5):730-738.
[23]
LIU Q Y, WANG X L. Strategies for the development of drugs targeting novel coronavirus 2019-nCoV[J]. Acta Pharm Sin(药学学报),2020,55(2):181-188.
[24]
KUBA K, IMAI Y, RAO S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury[J]. Nat Med, 2005, 11(8):875-879.
[25]
LI H, TAN X C, JIANG D, et al. Research progress on coronavirus and its therapeutic drugs[J]. Chin Pharm J(中国药学杂志),2020, 55(4):284-292.
2020, Vol. 55 
