Coronaviruses and Integrin αvβ3: Does Thyroid Hormone Modify the Relationship?

Abstract

BACKGROUND:

Uptake of coronaviruses by target cells involves binding of the virus by cell ectoenzymes. For the etiologic agent of COVID-19 (SARS-CoV-2), a receptor has been identified as angiotensin-converting enzyme-2 (ACE2). Recently it has been suggested that plasma membrane integrins may be involved in the internalization and replication of clinically important coronaviruses. For example, integrin αvβ3 is involved in the cell uptake of a model porcine enteric α-coronavirus that causes human epidemics. ACE2 modulates the intracellular signaling generated by integrins.

OBJECTIVE:

We propose that the cellular internalization of αvβ3 applies to uptake of coronaviruses bound to the integrin, and we evaluate the possibility that clinical host T4 may contribute to target cell uptake of coronavirus and to the consequence of cell uptake of the virus.

DISCUSSION AND CONCLUSIONS:

The viral binding domain of the integrin is near the Arg-Gly-Asp (RGD) peptide-binding site and RGD molecules can affect virus binding. In this same locale on integrin αvβ3 is the receptor for thyroid hormone analogues, particularly, L-thyroxine (T4). By binding to the integrin, T4 has been shown to modulate the affinity of the integrin for other proteins, to control internalization of αvβ3 and to regulate the expression of a panel of cytokine genes, some of which are components of the 'cytokine storm' of viral infections. If T4 does influence coronavirus uptake by target cells, other thyroid hormone analogues, such as deaminated T4 and deaminated 3,5,3'-triiodo-L-thyronine (T3), are candidate agents to block the virus-relevant actions of T4 at integrin αvβ3 and possibly restrict virus uptake.

• Authors: Paul J Davis, Hung-Yun Lin, Aleck Hercbergs, Kelly A Keating, Shaker A Mousa
• Journal: Endocrine research (Endocr Res) Vol. 45 Issue 3 Pg. 210-215 (Aug 2020) ISSN: 1532-4206 [Electronic] England
• PMID: 32628899 (Publication Type: Journal Article, Review)

Chemical References

• Cytokines
• Integrin alphaVbeta3
• Oligopeptides
• Receptors, Virus
• Thyroid Hormones
• arginyl-glycyl-aspartic acid
• Peptidyl-Dipeptidase A
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2
• Thyroxine

Topics

• Angiotensin-Converting Enzyme 2
• Animals
• Betacoronavirus (metabolism)
• Binding Sites
• COVID-19
• Coronavirus Infections (virology)
• Cytokines (physiology)
• Epithelial Cells (virology)
• Humans
• Integrin alphaVbeta3 (metabolism)
• Oligopeptides (metabolism)
• Pandemics
• Peptidyl-Dipeptidase A (metabolism)
• Pneumonia, Viral (virology)
• Porcine epidemic diarrhea virus (metabolism)
• Receptors, Virus (chemistry, drug effects, metabolism)
• SARS-CoV-2
• Swine
• Thyroid Hormones (pharmacology, physiology)
• Thyroxine (physiology)
• Virus Internalization