Host cell entry mediators implicated in the cellular tropism of SARS‑CoV‑2, the pathophysiology of COVID‑19 and the identification of microRNAs that can modulate the expression of these mediators (Review)

Katopodis,Periklis; Randeva,Harpal S.; Spandidos,Demetrios A.; Saravi,Sayeh; Kyrou,Ioannis; Karteris,Emmanouil

doi:10.3892/ijmm.2021.5075

Host cell entry mediators implicated in the cellular tropism of SARS‑CoV‑2, the pathophysiology of COVID‑19 and the identification of microRNAs that can modulate the expression of these mediators (Review)

Authors:
- Periklis Katopodis
- Harpal S. Randeva
- Demetrios A. Spandidos
- Sayeh Saravi
- Ioannis Kyrou
- Emmanouil Karteris
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Affiliations: Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK, Warwickshire Institute for The Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK, Laboratory of Clinical Virology, Medical School, University of Crete, 71409 Heraklion, Greece
Published online on: December 20, 2021 https://doi.org/10.3892/ijmm.2021.5075
Article Number: 20
Copyright: © Katopodis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The pathophysiology of coronavirus disease 2019 (COVID‑19) is mainly dependent on the underlying mechanisms that mediate the entry of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) into the host cells of the various human tissues/organs. Recent studies have indicated a higher order of complexity of the mechanisms of infectivity, given that there is a wide‑repertoire of possible cell entry mediators that appear to co‑localise in a cell‑ and tissue‑specific manner. The present study provides an overview of the ‘canonical’ SARS‑CoV‑2 mediators, namely angiotensin converting enzyme 2, transmembrane protease serine 2 and 4, and neuropilin‑1, expanding on the involvement of novel candidates, including glucose‑regulated protein 78, basigin, kidney injury molecule‑1, metabotropic glutamate receptor subtype 2, ADAM metallopeptidase domain 17 (also termed tumour necrosis factor‑α convertase) and Toll‑like receptor 4. Furthermore, emerging data indicate that changes in microRNA (miRNA/miR) expression levels in patients with COVID‑19 are suggestive of further complexity in the regulation of these viral mediators. An in silico analysis revealed 160 candidate miRNAs with potential strong binding capacity in the aforementioned genes. Future studies should concentrate on elucidating the association between the cellular tropism of the SARS‑CoV‑2 cell entry mediators and the mechanisms through which they might affect the clinical outcome. Finally, the clinical utility as a biomarker or therapeutic target of miRNAs in the context of COVID‑19 warrants further investigation.

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