Angiotensin Converting Enzyme 2 in Coronavirus Disease (COVID-19): Evidence from Bioinformatics Analysis

Abstract

Recently, the outbreak of coronavirus disease 2019 (COVID-19) is threatening human health globally. There is a dire need to find potential therapeutic agents. Angiotensin converting enzyme 2 (ACE2), as an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered as potential therapeutic target in COVID-19 pandemic. Here, our bioinformatics analysis revealed that the biological function of ACE2 was correlated with regulation of blood pressure and mediation of SARS-CoV-2 entry into host cells. Ten ACE2 cooperative proteins were identified by using STRING with a high score. ACE2 expressed highly in the small intestine, testis, and kidney. The level of ACE2 expression in tumor tissues varies in different types of cancers compared with that in normal tissues. It was worth noting that the expression level of ACE2 in the tumor has no effect on patient survival. MiRNA hsa-miR-942-5p, and three transcription factors (TFs) including Signal transducer and activator of transcription 4 (STAT4), Estrogen related receptor α (ESRRA), and Signal transducer and activator of transcription 3 (STAT3) were selected as novel ACE2 regulators. Moreover, nine potential therapeutic drugs were predicted by two online databases. Thus, our research may expand the overall view of ACE2 in COVID-19 treatment.

A computational and bioinformatic analysis of ACE2: an elucidation of its dual role in COVID-19 pathology and finding its associated partners as potential therapeutic targets

“…This disease presented several symptoms such as cough, fever, occasional diarrhea and pneumonia (Guan, Ni et al 2020 ; Holshue, DeBolt et al 2020 ; Huang, Wang et al 2020 ). Consequently, the whole-genome sequencing depicted the causative agent to be a member of the coronavirus family and named as 2019-nCoV by World Health Organization (WHO) initially (Wu, Zhao et al 2020 ; Zhou, Yang et al 2020 ; Zhu, Zhang et al 2020 ). However, the virus was officially designated as SARS-CoV-2 by International Committee on Taxonomy of Viruses later on (Gorbalenya, Baker et al 2020 ).…”

“…Coronaviruses (CoVs) are enveloped viruses containing positive-sense single-stranded RNA as their genetic material (Lai 2007 ; Lu and Liu 2012 ). The phylogenetic analyses of its genome indicated SARS-CoV-2 as a member of the genus Betacoronavirus , which also includes SARS-CoV, SARSr-CoV, MERS-CoV and many other viruses as well reported to have been isolated from humans and other animal species (Li, Li et al 2005 ; Lu, Zhao et al 2020 ; Wu, Zhao et al 2020 , Zhou, Yang et al 2020 ; Zhu, Zhang et al 2020 ). Although SARS-CoV-2 shares more than 93.1% sequence similarity of spike (S) gene with of BatCoV RaTG13, the similarity percentage with SARS-CoV and other SARSr-CoVs has been exhibited to be lower than 80% (Zhou, Yang et al 2020 ).…”

“…This receptor recognition is a significant checkpoint in determining the host range and cross-species viral infection. In this regard, angiotensin converting enzyme 2 (ACE2) has been recognized as a cellular receptor for SARS-CoV-2 spike protein (Zhou, Yang et al 2020 ). Initially, ACE2 was identified as an exopeptidase being expressed in vascular endothelial cells of heart and kidney where it catalyzes the conversion of angiotensins into its various forms (Donoghue, Hsieh et al 2000 ; Ferrario, Trask et al 2005 ).…”

“…On the other hand, although ACE2 is expressed in most of the vertebrates but all ACE2 forms cannot be utilized as receptors by SARS-CoV-2. For example, recent investigations have indicated that SARS-CoV-2 can infect Chinese horseshoe bats, swine and civet but cannot use mouse ACE2 receptor for its entry thereby presenting specificity to some species and not others (Zhou, Yang et al 2020 ).…”

“…When S1 binds to ACE2, another cleavage site is exposed on S2 which gets cleaved from host protease, a critical process for viral infection (Simmons, Gosalia et al 2005 ; Belouzard, Chu et al 2009 ; Millet and Whittaker 2015 ). The computational modeling (Lu, Zhao et al 2020 ; Xu, Chen et al 2020 ) and other experiments of viral infection using HeLa cells (Zhou, Yang et al 2020 ) have provided the evidences of ACE2 as receptor for SARS-CoV-2. Cryo-EM experiments have indicated that SARS-CoV-2 exhibited 10 time more affinity for ACE2 compared to SARS-CoV, which is also consistent with higher SARS-CoV-2 infection efficiency (Wrapp, Wang et al 2020 ).…”