Coronavirus Receptors as Immune Modulators

Devarakonda, Charan; Meredith, Emily; Ghosh, Monisha; Shapiro, Linda H.

doi:10.4049/jimmunol.2001062

Cited by 18 publications

(13 citation statements)

References 118 publications

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“…We evaluated the performance of phage mimicry using representatives of major classes of cell surface receptors, which mediate entry of coronaviruses into the host cells: (1) metallopeptidases, including angiotensin-converting enzyme 2 (ACE2) [1,26], and (2) growth factor receptors, including fibroblast growth factor receptor 3 (FGFR3) [35,37,[78][79][80][81].…”

Section: Landscape Phage Librariesmentioning

confidence: 99%

“…The evolution of the SARS-CoV-2 virus during the COVID-19 pandemic was accompanied by the emergence of a diverse assortment of new virus variants having multiple mutations in both receptor-and antibody-binding sites located throughout the spike S protein (Figure 1). Analysis of a variety of coronavirus variants that caused epidemics during the last 60 years showed that their evolution may occur not only through the appearance and selection of immuno-resistant mutants, but also by the selection of variants with altered spike proteins that can use alternative, or "reserve", human host receptors for entering into target cells [18,[26][27][28][29]. Our current understanding of the molecular mechanisms of virus adaptation to human host cells [30] and immuno-resistant human populations is not sufficient to rationally design efficient countermeasures against viral pandemics, such as the SARS-CoV-2 virus.…”

Section: Introductionmentioning

confidence: 99%

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Phage-Displayed Mimotopes of SARS-CoV-2 Spike Protein Targeted to Authentic and Alternative Cellular Receptors

Petrenko

Gillespie

Plano

et al. 2022

Viruses

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The evolution of the SARS-CoV-2 virus during the COVID-19 pandemic was accompanied by the emergence of new heavily mutated viral variants with increased infectivity and/or resistance to detection by the human immune system. To respond to the urgent need for advanced methods and materials to empower a better understanding of the mechanisms of virus’s adaptation to human host cells and to the immuno-resistant human population, we suggested using recombinant filamentous bacteriophages, displaying on their surface foreign peptides termed “mimotopes”, which mimic the structure of viral receptor-binding sites on the viral spike protein and can serve as molecular probes in the evaluation of molecular mechanisms of virus infectivity. In opposition to spike-binding antibodies that are commonly used in studying the interaction of the ACE2 receptor with SARS-CoV-2 variants in vitro, phage spike mimotopes targeted to other cellular receptors would allow discovery of their role in viral infection in vivo using cell culture, tissue, organs, or the whole organism. Phage mimotopes of the SARS-CoV-2 Spike S1 protein have been developed using a combination of phage display and molecular mimicry concepts, termed here “phage mimicry”, supported by bioinformatics methods. The key elements of the phage mimicry concept include: (1) preparation of a collection of p8-type (landscape) phages, which interact with authentic active receptors of live human cells, presumably mimicking the binding interactions of human coronaviruses such as SARS-CoV-2 and its variants; (2) discovery of closely related amino acid clusters with similar 3D structural motifs on the surface of natural ligands (FGF1 and NRP1), of the model receptor of interest FGFR and the S1 spike protein; and (3) an ELISA analysis of the interaction between candidate phage mimotopes with FGFR3 (a potential alternative receptor) in comparison with ACE2 (the authentic receptor).

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Section: Landscape Phage Librariesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phage-Displayed Mimotopes of SARS-CoV-2 Spike Protein Targeted to Authentic and Alternative Cellular Receptors

Petrenko

Gillespie

Plano

et al. 2022

Viruses

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“…CD13, CD24, and CD82 are involved in inflammatory processes (Barkal et al., 2019; Lu et al., 2020; Yeung et al., 2018). CD13 is known receptor for several corona viruses (Devarakonda et al., 2021; Nomura et al., 2004; Pöhlmann et al., 2006; Qi et al., 2020) and associated with several EVs types, including ones from, that is, synoviocytes, endometrial epithelial cells, microglia, urine, plasma, leukocytes and umbilical cord‐derived mesenchymal stromal cells (Erdbrügger et al., 2021; Lin et al., 2020; Morgan et al., 2016; Priya et al., 2021; Potolicchio et al., 2005; Romanov et al., 2018; Tőkés‐Füzesi et al., 2018; Yoshihara et al., 2021). The tetraspanin CD82 is a constituent of tetraspanin‐enriched membrane domains (TEMs, which represent the places of entry/egress of some viruses) but also responsible for immune cells recruitment, migration (Yeung et al., 2018) and acts as a costimulatory molecule for T cells (Earnest et al., 2017; Florin & Lang, 2018; ProteinAtlas: CD82; Sims et al., 2018; Yáñez‐Mó et al., 2009).…”

Section: Resultsmentioning

confidence: 99%

Serum‐derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID‐19 patients

Tertel

Tomić

Đokić

et al. 2022

J of Extracellular Vesicle

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COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13 + and CD82 + EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC + EVs than sera of the healthy donors and more CD24 + EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.

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“…However, some mild patients also experienced a cytokine storm due to immune disorders. This involves a suicide attack that can damage the virus but also leave behind collateral damage, which will eventually lead to further lung injury, multiple organ failure and even increase the risk of death ( 96 ). Therefore, monitoring the level of pro-inflammatory cytokines and taking corresponding intervention measures as early as possible is of great significance to delay the transformation of mild or moderate patients to severe patients and also to achieve good clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Research Progress in the Treatment of Complications and Sequelae of COVID-19

et al. 2021

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With the improvement in the understanding of COVID-19 and the widespread vaccination of COVID-19 vaccines in various countries, the epidemic will be brought under control soon. However, multiple viruses could result in the post-viral syndrome, which is also common among patients with COVID-19. Therefore, the long-term consequences and the corresponding treatment of COVID-19 should be the focus in the post-epidemic era. In this review, we summarize the therapeutic strategies for the complications and sequelae of eight major systems caused by COVID-19, including respiratory system, cardiovascular system, neurological system, digestive system, urinary system, endocrine system, reproductive system and skeletal complication. In addition, we also sorted out the side effects reported in the vaccine trials. The purpose of this article is to remind people of possible complications and sequelae of COVID-19 and provide robust guidance on the treatment. It is extremely important to conduct long-term observational prognosis research on a larger scale, so as to have a comprehensive understanding of the impact of the SARS-CoV-2 on the human body and reduce complications to the greatest extent.

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Coronavirus Receptors as Immune Modulators

Cited by 18 publications

References 118 publications

Phage-Displayed Mimotopes of SARS-CoV-2 Spike Protein Targeted to Authentic and Alternative Cellular Receptors

Phage-Displayed Mimotopes of SARS-CoV-2 Spike Protein Targeted to Authentic and Alternative Cellular Receptors

Serum‐derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID‐19 patients

Research Progress in the Treatment of Complications and Sequelae of COVID-19

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