scholarly journals The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

2020 ◽  
Author(s):  
Hao Zhang ◽  
Zijian Kang ◽  
Haiyi Gong ◽  
Da Xu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Digestive System ◽  
Bioinformatics Analysis ◽  
Cell Receptor ◽  
Host Cells ◽  
Converting Enzyme ◽  
Significant Public Health ◽  
Novel Coronavirus ◽  
Absorptive Enterocytes ◽  
Policy Setting

AbstractSince December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.

scholarly journals Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process

Gut ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1010-1018 ◽  
Author(s):  
Hao Zhang ◽  
Zijian Kang ◽  
Haiyi Gong ◽  
Da Xu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Viral Entry ◽  
Digestive System ◽  
Cell Types ◽  
Cell Receptor ◽  
Host Cells ◽  
Target Cells ◽  
Sequencing Data ◽  
Transmembrane Serine Protease ◽  
Coexpression Pattern

ObjectiveSince December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed.DesignFive datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion.ResultsCell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon.ConclusionThis study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.

scholarly journals Increasing Host Cellular Receptor—Angiotensin-Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019-nCoV Infection

2020 ◽  
Author(s):  
Pei-Hui Wang ◽  
Yun Cheng
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Emerging Infectious Diseases ◽  
Cell Receptor ◽  
Host Cells ◽  
Cellular Receptor ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Coronavirus Infection ◽  
Entry Receptor

AbstractThe ongoing outbreak of a new coronavirus (2019-nCoV) causes an epidemic of acute respiratory syndrome in humans. 2019-nCoV rapidly spread to national regions and multiple other countries, thus, pose a serious threat to public health. Recent studies show that spike (S) proteins of 2019-nCoV and SARS-CoV may use the same host cell receptor called angiotensin-converting enzyme 2 (ACE2) for entering into host cells. The affinity between ACE2 and 2019-nCoV S is much higher than ACE2 binding to SARS-CoV S protein, explaining that why 2019-nCoV seems to be more readily transmitted from the human to human. Here, we reported that ACE2 can be significantly upregulated after infection of various viruses including SARS-CoV and MERS-CoV. Basing on findings here, we propose that coronavirus infection can positively induce its cellular entry receptor to accelerate their replication and spread, thus drugs targeting ACE2 expression may be prepared for the future emerging infectious diseases caused by this cluster of viruses.

scholarly journals ACE-2-derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2

2020 ◽  
Author(s):  
Saroj Kumar Panda ◽  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Abhik Kumar Ray ◽  
Malay Kumar Rana
Keyword(s):  
Principal Component ◽  
Host Cells ◽  
Spike Protein ◽  
Peptide Inhibitor ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Inhibition Assay ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus

<p>SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein-hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields two-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide-inhibitor of the novel coronavirus. The binding of the spike protein and the best peptide-inhibitor with hACE-2 is explored further by molecular dynamics, free energy, and principal component analysis to demonstrate its efficacy. Further, the inhibition assay study with the best peptide inhibitor is in progress. </p>

scholarly journals Can Levamisole be used in the treatment of COVID-19 patients presenting with diarrhea?

2020 ◽  
Vol 14 (08) ◽  
pp. 844-846
Author(s):  
Oğuz Abdullah Uyaroğlu ◽  
Gülay Sain Güven ◽  
İbrahim Güllü
Keyword(s):  
Antiviral Drug ◽  
Cell Receptor ◽  
Host Cells ◽  
Converting Enzyme ◽  
Immunomodulatory Effects ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
The World ◽  
Glandular Cells ◽  
A Cell

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China, on Jan 7, 2020. Over the following months, the virus rapidly spread throughout the world. Coronavirus Disease 2019 (COVID-19) can involve the gastrointestinal tract, including symptoms like nausea, vomiting and diarrhea and shedding of the SARS-CoV-2 in feces. Angiotensin-converting enzyme 2 (ACE2) protein, which has been proven to be a cell receptor for SARS-CoV-2, is expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells. According to the literature, rates of COVID-19 patients reporting diarrhea were between 7 - 14%. Diarrhea in the course of COVID-19 disease can cause dehydration and hospitalization. Although no antiviral drug was specifically designed for the treatment of diarrhea, several molecules could have beneficial effects by reducing viral replication. In this letter, we discussed the Levamisole, which is an anthelmintic agent with immunomodulatory effects, could be used effectively both for antiviral therapy and especially in COVID-19 patients with diarrhea.

scholarly journals Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3980 ◽  
Author(s):  
Muchtaridi Muchtaridi ◽  
M. Fauzi ◽  
Nur Kusaira Khairul Ikram ◽  
Amirah Mohd Gazzali ◽  
Habibah A. Wahab
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Host Cells ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Mortality And Morbidity ◽  
Angiotensin Converting Enzyme 2 ◽  
Arterial Blood ◽  
Potential Efficacy ◽  
Novel Coronavirus

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.

scholarly journals An Investigation of the Expression of 2019 Novel Coronavirus Cell Receptor Gene ACE2 in a Wide Variety of Human Tissues

2020 ◽  
Author(s):  
Mengyuan Li ◽  
Lin Li ◽  
Yue Zhang ◽  
Xiaosheng Wang
Keyword(s):  
Blood Vessel ◽  
Older Persons ◽  
Digestive System ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Expression Levels ◽  
Normal Tissues ◽  
Immune Signatures ◽  
Males And Females ◽  
Novel Coronavirus

Abstract Background: The 2019 novel coronavirus (2019-nCoV) has affected more than 72,000 people worldwide and caused more than 1,800 deaths so far. 2019-nCoV uses the angiotensinconverting enzyme 2 (ACE2) as the cell receptor to invade the human host and primarily causes pneumonia. Thus, ACE2 is the key to understanding the mechanism of 2019-nCoV infection. Methods: We compared ACE2 expression levels across 31 human normal tissues, between males and females, and between younger (ages <= 49 years) and older (ages > 49 years) persons in these tissues. We also investigated the correlations between ACE2 expression and immune signatures in various tissues. Results: ACE2 expression levels were the highest in small intestine, testis, kidney, heart, thyroid, and adipose tissue, and were the lowest in blood, spleen, bone marrow, brain, blood vessel, and muscle. In lungs, colon, liver, bladder, and adrenal gland, ACE2 showed the medium expression levels. ACE2 was not differentially expressed between males and females and between younger and older persons in any tissue. In skin, digestive system, brain, and blood vessel, ACE2 expression levels were positively associated with immune signatures in both males and females. In thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively.Conclusions: Our data provide potential cues for the 2019-nCoV epidemic may infect other tissues outside lungs, affect males and females and young and old persons equally, and old age and male are associated with higher mortality risk for 2019-nCoV infection.

scholarly journals Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor

2020 ◽  
Author(s):  
Sanchita Hati ◽  
Sudeep Bhattacharyya
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Binding Affinity ◽  
Disulfide Bonds ◽  
Host Cells ◽  
Converting Enzyme ◽  
Dynamic Simulations ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
The Impact ◽  
Spike Proteins

AbstractThe novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress.

scholarly journals The Significance of Angiotensin-Converting Enzyme-2 (ACE2) in SARSCov-2 Infection and COVID-19

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Carolina Restini ◽  
Trevor Belavek ◽  
Rafael Bernal ◽  
Vanessa Ibrahim ◽  
Kelly Irwin ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Cell Receptor ◽  
Host Cells ◽  
World Health ◽  
Protective Effects ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Health Organization

: The new coronavirus was first reported in 2019 (China) and officially announced by the World Health Organization as a pandemic in March 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pneumonia-associated illnesses and shares structural homology with the related Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1). One of the mechanisms for SARS-Cov-1 and -2 infection is mediated by the angiotensin-converting enzyme-2 (ACE2) cell receptor, enabling the virus to enter the host cells. ACE2 is an isoform of the angiotensin-converting enzyme 1 (ACE). The actions of ACE2 counterbalance the classic renin-angiotensin system (RAS) axis through the production of Ang 1-7, which promotes cardiovascular, renal, and lung-protective effects. The ACE2 is not the only route for SARS-CoV-2 to enter the host cells. However, due to its roles in the RAS and its participation in the SARS-CoV-2 virulence, ACE2 has gained attention regarding viral mechanisms of pathogenesis, effects of drugs that interfere with the RAS, and as a potential target for therapeutic strategies for the damages caused by SARSCoV-2 infection. Among other tissues, ACE2 gene expression seems to be increased in the lungs upon SARS-CoV-2 infection; however, amid other variables, expression and/or activity of ACE2 is shown as a disease, sex, and age-dependent. The present review covers critical aspects for a comprehensive understanding of ACE2 and its current involvement in SARS-CoV-2 infection and the development of COVID-19.

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