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ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology.

ABSTRACT: The 2019-nCoV is a rapidly contagious pneumonia caused by the recently discovered coronavirus. Although generally the most noticeable symptoms are concentrated in the lungs, the disorders in the gastrointestinal tract are of great importance in the diagnosis of 2019-nCoV. The angiotensin-converting enzyme 2 (ACE2), an important regulator of many physiological functions, including blood pressure and nutrients absorption, is recently identified as a vital entry for 2019-nCoV to enter host cells. In this review, we summarize its functions both physiologically and pathologically. We also elaborate its conflicting roles from the clews of contemporary researches, which may provide significant indications for pharmacological investigations and clinical uses.

SUBMITTER: Guo Y

PROVIDER: S-EPMC8493804 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology.

Guo Yuexin Y Wang Boya B Gao Han H Gao Lei L Hua Rongxuan R Xu Jing-Dong JD

Frontiers in molecular biosciences 20210921

The 2019-nCoV is a rapidly contagious pneumonia caused by the recently discovered coronavirus. Although generally the most noticeable symptoms are concentrated in the lungs, the disorders in the gastrointestinal tract are of great importance in the diagnosis of 2019-nCoV. The angiotensin-converting enzyme 2 (ACE2), an important regulator of many physiological functions, including blood pressure and nutrients absorption, is recently identified as a vital entry for 2019-nCoV to enter host cells. I ...[more]

PMID: 34631794

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Project description:BackgroundOn March 11, 2020, the World Health Organization (WHO) officially announced that the coronavirus disease 2019 (COVID-19) had reached global pandemic status. Current studies have found that angiotensin-converting enzyme 2 (ACE2) is a cell surface receptor of the novel coronavirus that plays a vital role in the pathogenesis of COVID-19. It is of immense importance for the prevention of virus transmission and treatment to clarify the distribution and expression of ACE2 in various tissues and organs of the body.MethodsRNAseq transcriptome data and sex data were obtained from the genotype-tissue expression (GTEx) and the Cancer Genome Atlas (TCGA) databases. We separately analyzed the distribution of ACE2 expression in different tissues in the GTEx and TCGA database, and explored the correlation between sex and ACE2 expression levels. Next, the expression levels of ACE2 in different tissues and organs and its correlation with sex were analyzed once again after combing all samples from the two databases.ResultsACE2 expression data were collected from the GTEx database for 6738 normal tissues. Six hundred eighteen tumor tissue data were collected from the TCGA database. The results of the analysis are consistent from different databases. The results indicated that the expression of ACE2 was the highest in the small intestines, higher in tissues such as salivary glands in the testicular, kidney, heart, thyroid and adipose tissues, while the expression of ACE2 was lower in tissues such as the spleen, brain, muscle, pituitary, and skin. There were no significant differences in the expression of ACE2 in the different organs when it came to the individual's sex.ConclusionsOur study deeply explored the distribution and expression of ACE2 in various tissues of the human body. The tissues and organs with high ACE2 expression were consistent with the current clinical and basic research results of the novel coronavirus. Our study is conducive to the discovery of potential target organs for viral infection, to provide a reference for the development of clinical progress of patients with novel coronavirus infection.

Project description:ContextSince the outbreak of COVID-19 in 2019, the 2019-nCov coronavirus has appeared diverse mutational characteristics due to its own flexible conformation. One multiple-mutant strain (Omicron) with surprisingly infective activity outburst, and affected the biological activities of current drugs and vaccines, making the epidemic significantly difficult to prevent and control, and seriously threaten health around the world. Importunately exploration of mutant characteristics for novel coronavirus Omicron can supply strong theoretical guidance for learning binding mechanism of mutant viruses. What's more, full acknowledgement of key mutated-residues on Omicron strain can provide new methodology of the novel pathogenic mechanism to human ACE2 receptor, as well as the subsequent vaccine development.MethodsIn this research, 3D structures of 32 single-point mutations of 2019-nCov were firstly constructed, and 32-sites multiple-mutant Omicron were finally obtained based one the wild-type virus by homology modeling method. One total number of 33 2019-nCov/ACE2 complex systems were acquired by protein-protein docking, and optimized by using preliminary molecular dynamic simulations. Binding free energies between each 2019-nCov mutation system and human ACE2 receptor were calculated, and corresponding binding patterns especially the regions adjacent to mutation site were analyzed. The results indicated that one total number of 6 mutated sites on the Omicron strain played crucial role in improving binding capacities from 2019-nCov to ACE2 protein. Subsequently, we performed long-term molecular dynamic simulations and protein-protein binding energy analysis for the selected 6 mutations. 3 infected individuals, the mutants T478K, Q493R and G496S with lower binding energies -66.36, -67.98 and -67.09 kcal/mol also presents the high infectivity. These findings indicated that the 3 mutations T478K, Q493R and G496S play the crucial roles in enhancing binding affinity of Omicron to human ACE2 protein. All these results illuminate important theoretical guidance for future virus detection of the Omicron epidemic, drug research and vaccine development.

Dataset Information

ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology.

Publications

ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology.

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