Possible inhibitors of ACE 2 , the receptor of 2019-nCoV

Possible inhibitors of ACE2, the receptor of 2019-nCoV Chuanbo Huang, Xiangwen Ji, Wanlu Zhou, Fenghong Zhang, Liang Wang, Qinghua Cui Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Beijing, 100191, China Co., Ltd of JeaMoon Technology, 6 Rd Middle Zuojiazhuang, Beijing, 100028, China.


Introduction
In the end of 2019, some patients with severe febrile respiratory illness were admitted to a hospital in Wuhan, Hubei Province, China. However, no known pathogens were detected in the clinical specimens from these patients [1]. Quickly, sequencing to the RNA extracted from bronchoalveolar-lavage fluid from the patients revealed a novel coronavirus, designated as 2019-nCoV, which belong to the lineage B of the genus betacoronavirus [1]. The virus seems spreads rapidly. As of January 24, 2020, more than 800 cases have been reported and the mortality rate is about 3% [2]. China made a quick response including active case finding, improve public awareness, and sharing sequence information, which provides helps in the patient monitoring, diagnostics and prevention of 2019-nCoV [3,4]. However, a number of key questions remain to be explored [4], for example the virus's origin and cross-species transmission, its ability of spread, the extend of interhuman transmission, and the spectrum of clinical disease.
To address these important questions and issues, the global scientific community also has a quick response. For example, the detection of 2019-nCoV has achieved good advances [5].
In addition, clinical features of patients infected with 2019-nCoV were revealed [6]. Moreover, a number of computational analysis and modeling have been performed to explore the origin, infectivity, and cross-species transmission [7,8,9], evolution [10], transmission patterns and rules [11,12,13,14,15]. These studies provided helps in better understanding the origin, evolution, and transmission of 2019-nCoV.
However, one of the most important questions is that current treatments for 2019-nCoV are empirical [6] and there are still no efficient antiviral therapies [2]. Moreover, we also failed However, before the identification of efficient drugs, the development of more possible therapeutic strategies is still emergently needed. Like SARS-CoV, 2019-nCoV also belongs to the lineage B of the genus betacoronavirus. It thus appears that as SARS-CoV, the human angiotensin-converting enzyme 2 (ACE2) is also the receptor for 2019-nCoV's entry into lower respiratory tract epithelial cells [2]. This was recently confirmed by Letko and Munster [16]. Given that ACE2 is a key human gene for 2019-nCoV' infection to human, it is thus expected that approaches decreasing ACE2 expression could has anti-2019-nCoV activities.
Based on the above observations, here we screened potential agents decreasing ACE2 expression using two databases, Connectivity Map

Datasets of gene expression profiles induced by drugs and other agents
From Connectivity Map [17] (CMap, version 2.0), we obtained the gene expression profiles

Screening agents decreasing ACE2 expression
We used the normalized gene expression datasets. A cutoff of fold change (FC) 2.0 was selected to determine whether ACE2 is significantly decreased by a putative agent or not.
Then, we screened CMap and JMap using a single-gene screening module in the JeaMoon DrugMine software platform.

The CMap compounds that decrease ACE2 expression
As a result, CMap analysis identified 5 compounds that functionally decrease the expression level of ACE2 (Fig 1), potential health hazard, toxicity, and side effects.

The JMap agents that decrease ACE2 expression
As a result, JMap analysis identified a number of agents that functionally decrease the expression level of ACE2 (Fig 2). These agents include traditional Chinese Medicine (TCM), compound, and biologics (Fig 2). The 4 TCM showed significant ability to decrease ACE2 expression, especially Andrographis (FC=21.57), Urtica (FC=11.59), and Sambucus (5.99).
Indeed, some studies reported potential effects of anti-pneumonia for active ingredients from Andrographis [18,19], Urtica [20], Sambucus [21], and Astragalus [22]. This finding suggests that the four TCM could be possible anti-2019-nCoV therapies. For the small molecules, we found literature that some predicted compounds can mitigate pneumonia or lung injury, including valproic acid [23], butyrate [24], epoxomicin [25], and emetine [26]. Because arsenic trioxide shows significant toxicity, it should be carefully to test its possibility. Interestingly, nicotine shows an ability of decreasing ACE2 expression, suggesting a possible role of anti-2019-nCoV. This finding may be consistent with our previous report that smoking-inhibited miRNAs are significantly associated with SARS [27]. For the biologics, previous reports supported the prediction for lipopolysaccharide [28]. We previously found oxLDL has protective roles in influenza virus infection [29], suggesting that oxLDL could be a protective factor for 2019-nCoV infection, as predicted here.

DISCUSSION
The recent outbreak 2019-nCoV infection brings a new severe problem for public health.
The unavailability of efficient therapeutic strategies is one of the most important questions at