Do Changes in ACE-2 Expression Affect SARS-CoV-2 Virulence and Related Complications: A Closer Look into Membrane-Bound and Soluble Forms

Yalcin, Huseyin C.; Sukumaran, Vijayakumar; Al-Ruweidi, Mahmoud Khatib A A; Shurbaji, Samar

doi:10.3390/ijms22136703

Cited by 35 publications

(30 citation statements)

References 99 publications

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“…This region is reported to be the most essential for viral attachment and entry into the host cells [44,45]. Therefore, ACE2 expression in different tissues and interactions with SARS-CoV-2 are critical for the infection's progression to severe coronavirus disease 2019 (COVID-19) [46]. The P314L mutation in NSP12 (RNA-dependent polymerase) may play a causal role in viral replication, therefore enhancing its transmission ability and infectivity [44].…”

Section: Discussionmentioning

confidence: 99%

Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect?

Menasria

Aguilera

2022

Microorganisms

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Here, we report a first comprehensive genomic analysis of SARS-CoV-2 variants circulating in North African countries, including Algeria, Egypt, Libya, Morocco, Sudan and Tunisia, with respect to genomic clades and mutational patterns. As of December 2021, a total of 1669 high-coverage whole-genome sequences submitted to EpiCoV GISAID database were analyzed to infer clades and mutation annotation compared with the wild-type variant Wuhan-Hu-1. Phylogenetic analysis of SARS-CoV-2 genomes revealed the existence of eleven GISAID clades with GR (variant of the spike protein S-D614G and nucleocapsid protein N-G204R), GH (variant of the ORF3a coding protein ORF3a-Q57H) and GK (variant S-T478K) being the most common with 25.9%, 19.9%, and 19.6%, respectively, followed by their parent clade G (variant S-D614G) (10.3%). Lower prevalence was noted for GRY (variant S-N501Y) (5.1%), S (variant ORF8-L84S) (3.1%) and GV (variant of the ORF3a coding protein NS3-G251V) (2.0%). Interestingly, 1.5% of total genomes were assigned as GRA (Omicron), the newly emerged clade. Across the North African countries, 108 SARS-CoV-2 lineages using the Pangolin assignment were identified, whereby most genomes fell within six major lineages and variants of concern (VOC) including B.1, the Delta variants (AY.X, B.1.617.2), C.36, B.1.1.7 and B.1.1. The effect of mutations in SAR-CoV-2 genomes highlighted similar profiles with D614G spike (S) and ORF1b-P314L variants as the most changes found in 95.3% and 87.9% of total sequences, respectively. In addition, mutations affecting other viral proteins appeared frequently including; N:RG203KR, N:G212V, NSP3:T428I, ORF3a:Q57H, S:N501Y, M:I82T and E:V5F. These findings highlight the importance of genomic surveillance for understanding the SARS-CoV-2 genetic diversity and its spread patterns, leading to a better guiding of public health intervention measures. The know-how analysis of the present work could be implemented worldwide in order to overcome this health crisis through harmonized approaches.

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Section: Discussionmentioning

confidence: 99%

Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect?

Menasria

Aguilera

2022

Microorganisms

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“…Following this pre-incubation, the cells were treated with the same compound dilutions in MEM medium containing only 1% FCS, to prevent the inhibition of infection by components of FCS [ 12 ]. Moreover, soluble ACE2 can effectively block the binding of SARS-CoV S-protein to membrane-bond ACE2 and thereby prevents SARS-CoV entry [ 13 , 14 ], which is possibly transferable to SARS-CoV-2. Since FCS contains soluble ACE2, a reduced FCS concentration possibly intensifies the infection of Caco-2 cells [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

Characterization of ACE Inhibitors and AT1R Antagonists with Regard to Their Effect on ACE2 Expression and Infection with SARS-CoV-2 Using a Caco-2 Cell Model

Reus

Schneider

Ulshöfer

et al. 2021

Life

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Blood-pressure-lowering drugs are proposed to foster SARS-CoV-2 infection by pharmacological upregulation of angiotensin-converting enzyme 2 (ACE2), the binding partner of the virus spike (S) protein, located on the surface of the host cells. Conversely, it is postulated that angiotensin–renin system antagonists may prevent lung damage caused by SARS-CoV-2 infection, by reducing angiotensin II levels, which can induce permeability of lung endothelial barrier via its interaction with the AT1 receptor (AT1R). Methods: We have investigated the influence of the ACE inhibitors (lisinopril, captopril) and the AT1 antagonists (telmisartan, olmesartan) on the level of ACE2 mRNA and protein expression as well as their influence on the cytopathic effect of SARS-CoV-2 and on the cell barrier integrity in a Caco-2 cell model. Results: The drugs revealed no effect on ACE2 mRNA and protein expression. ACE inhibitors and AT1R antagonist olmesartan did not influence the infection rate of SARS-CoV-2 and were unable to prevent the SARS-CoV-2-induced cell barrier disturbance. A concentration of 25 µg/mL telmisartan significantly reduced the virus replication rate. Conclusion: ACE inhibitors and AT1R antagonist showed neither beneficial nor detrimental effects on SARS-CoV-2-infection and cell barrier integrity in vitro at pharmacologically relevant concentrations.

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“…However, others suggested that sACE2 might reduce the infection success of SARS-CoV-2 [ 15 ]. The multilevel interactions of ACE2 with SARS-CoV-2 -protein have been reviewed recently [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

OM-85 Broncho-Vaxom®, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells

et al. 2021

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In clinical studies, OM-85 Broncho-Vaxom®, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by human bronchial epithelial cells. Human bronchial epithelial cells were treated with OM-85 over 5 days. The expression of SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17) were determined by Western blotting and quantitative RT-PCR. Soluble (s)ACE2, heparan sulfate, heparanase, and hyaluronic acid were assessed by ELISA. OM-85 significantly reduced the expression of ACE2 (p < 0.001), TMPRSS2 (p < 0.001), DPP4 (p < 0.005), and cellular heparan sulfate (p < 0.01), while ADAM17 (p < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (p < 0.05), hyaluronic acid (p < 0.002), and hyaluronan synthase 1 (p < 0.01). Consequently, the infection by a SARS-CoV-2 spike protein pseudo-typed lentivirus was reduced in cells pretreated with OM-85. All effects of OM-85 were concentration- and time-dependent. The results suggest that OM-85 might reduce the binding of SARS-CoV-2 S-protein to epithelial cells by modification of host cell membrane proteins and specific glycosaminoglycans. Thus, OM-85 might be considered as an add-on for COVID-19 therapy.

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Do Changes in ACE-2 Expression Affect SARS-CoV-2 Virulence and Related Complications: A Closer Look into Membrane-Bound and Soluble Forms

Cited by 35 publications

References 99 publications

Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect?

Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect?

Characterization of ACE Inhibitors and AT1R Antagonists with Regard to Their Effect on ACE2 Expression and Infection with SARS-CoV-2 Using a Caco-2 Cell Model

OM-85 Broncho-Vaxom®, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells

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