A Review of Human Coronaviruses’ Receptors: The Host-Cell Targets for the Crown Bearing Viruses

Nassar, Aaya; Ibrahim, Ibrahim M.; Amin, Fatma G.; Magdy, Merna; Elgharib, Ahmed M; Azzam, Eman B.; Nasser, Filopateer; Yousry, Kirllos; Shamkh, Israa M; Mahdy, Samah M; Elfiky, Abdo A.

doi:10.3390/molecules26216455

Cited by 49 publications

(27 citation statements)

References 221 publications

(315 reference statements)

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“…Thus, although ACE2 is more highly expressed in adipose tissue than in the lungs [ 51 ], females may have reduced levels of ACE2 in WAT because of their higher levels of estrogen. However, SARS-CoV-2 can also infect and invade cells via other receptors and cellular mechanisms [ 34 , 52 ]. For example, SARS-CoV-2 can infect cells through the cholesterol-rich lipid rafts [ 53 , 54 , 55 ], which may be the case in adipose tissue in female mice.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of Fat Tissue to SARS-CoV-2 Infection in Female hACE2 Mouse Model

Thangavel

Dhanyalayam

Lizardo

et al. 2023

IJMS

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The coronavirus disease (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 has had a catastrophic effect globally causing millions of deaths worldwide and causing long-lasting health complications in COVID-19 survivors. Recent studies including ours have highlighted that adipose tissue can act as a reservoir where SARS-CoV-2 can persist and cause long-term health problems. Here, we evaluated the effect of SARS-CoV-2 infection on adipose tissue physiology and the pathogenesis of fat loss in a murine COVID-19 model using humanized angiotensin-converting enzyme 2 (hACE2) mice. Since epidemiological studies reported a higher mortality rate of COVID-19 in males than in females, we examined hACE2 mice of both sexes and performed a comparative analysis. Our study revealed for the first time that: (a) viral loads in adipose tissue and the lungs differ between males and females in hACE2 mice; (b) an inverse relationship exists between the viral loads in the lungs and adipose tissue, and it differs between males and females; and (c) CoV-2 infection alters immune signaling and cell death signaling differently in SARS-CoV-2 infected male and female mice. Overall, our data suggest that adipose tissue and loss of fat cells could play important roles in determining susceptibility to CoV-2 infection in a sex-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Susceptibility of Fat Tissue to SARS-CoV-2 Infection in Female hACE2 Mouse Model

Thangavel

Dhanyalayam

Lizardo

et al. 2023

IJMS

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“…Interaction of Lf with RGD-motif was well documented for TfR1 (Kawabata et al 1999 ) and extracellular matrix proteins i.e., fibronectin and vitronectin (Sakamoto et al 2006 ). Interestingly, 403 RGD 405 -motif in RBD of Spike protein is missing in previous human coronavirus variants, but remains conserved in SARS-CoV-2 strains (Liu et al 2020 ; Othman et al 2022 ; Nassar et al 2021 ). Considering the competitive effect of sTfR and synthetic RGD on the interaction of RBD with SARS-CoV-2-neutralizing mAb S6 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

et al. 2022

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The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R 2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by K D to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1–4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s10534-022-00458-6.

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“…Among the human TLR family, TLR3, TLR7, and TLR8 reside in the endosome compartment and can act as endosomal RNA sensors [ 38 ]. TLR3 mainly senses double-stranded viral RNA (dsRNA), including the genome of dsRNA viruses and intermediates produced during ssRNA replication, whereas TLR7 and TLR8 sense viral ssRNA and bacterial RNA [ 39 , 40 ]. TLR9 specifically recognizes cytosine–phosphate–guanine (CpG) motifs in the DNA of microbes and viruses [ 41 ].…”

Section: Aging and Immune Response In Covid-19mentioning

confidence: 99%

Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

Yiang

et al. 2023

Viruses

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Aging processes, including immunosenescence, inflammation, inflammasome formation, genomic instability, telomeric attrition, and altered autophagy, are involved in viral infections and they may contribute to increased pathophysiological responses to the SARS-CoV-2 infection in the elderly; this poses additional risks of accelerated aging, which could be found even after recovery. Aging is associated with oxidative damage. Moreover, SARS-CoV-2 infections may increase the production of reactive oxygen species and such infections will disturb the Ca++ balance via an endoplasmic reticulum (ER) stress-mediated unfolded protein response. Although vaccine development and anti-inflammation therapy lower the severity of COVID-19, the prevalence and mortality rates are still alarming in some countries worldwide. In this review, we describe the involvement of viral proteins in activating ER stress transducers and their downstream signals and in inducing inflammation and inflammasome formation. Furthermore, we propose the potential of melatonin as an ER stress modulator, owing to its antioxidant, anti-inflammatory, and immunoregulatory effects in viral infections. Considering its strong safety profile, we suggest that additive melatonin supplementation in the elderly could be beneficial in treating COVID-19.

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A Review of Human Coronaviruses’ Receptors: The Host-Cell Targets for the Crown Bearing Viruses

Cited by 49 publications

References 221 publications

Susceptibility of Fat Tissue to SARS-CoV-2 Infection in Female hACE2 Mouse Model

Susceptibility of Fat Tissue to SARS-CoV-2 Infection in Female hACE2 Mouse Model

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

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