Integrins as Therapeutic Targets for SARS-CoV-2

Authors

Timothy E. Gressett, Tulane University School of Medicine, Clinical Neuroscience Research Center (CNRC), New Orleans, LA, United States, Department of Neurology, Tulane University School of Medicine, New Orleans, LA, United States., Tulane Brain Institute, Tulane University, New Orleans, LA, United States
Danielle Nader, RCSI University of Medicine and Health Sciences, School of Pharmacy and Biomolecular Sciences (PBS), Dublin, Ireland
Juan Pablo Robles, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Juriquilla, Mexico.
Tione Buranda, University of New Mexico Health Sciences Center (HSC), Department of Pathology, Albuquerque, NM, United States.
Steven W. Kerrigan, RCSI University of Medicine and Health Sciences, School of Pharmacy and Biomolecular Sciences (PBS), Dublin, Ireland
Gregory Bix, Tulane University School of Medicine, Clinical Neuroscience Research Center (CNRC), New Orleans, LA, United States, Department of Neurology, Tulane University School of Medicine, New Orleans, LA, United States, Tulane Brain Institute, Tulane University, New Orleans, LA, United States

Document Type

Article

Publication Date

1-1-2022

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA virus of the genus Betacoronavirus. Its genome is composed of four structural proteins known as spike (S), envelope (E), membrane (M), and nucleocapsid (N), of which E, M, and N are integrated into the viral envelope. The S glycoprotein, which protrudes from the surface of mature virions as a spike, is essential for virus attachment, fusion, and entry into the host cell. While the relationship between the spike protein of SARS-CoV-2 and the angiotensin- converting enzyme 2 (ACE2) receptor has been readily established, the S1 subunit also contains a solvent-exposed arginine-glycine-aspartic acid (RGD) binding motif that is predominantly recognized by integrins, specifically a5b1 and aVb3 (Sigrist et al., 2020; Tresoldi et al., 2020). These integrins, which are primarily expressed on vascular endothelial cells, are part of a large family of heterodimeric transmembrane receptors containing an a and a b subunit and are devoted to cell adhesion to the extracellular matrix and other signaling effects and functions to include the immune response (Hynes, 2002). Blockade of SARS-CoV-2 binding to a5b1 and aVb3 integrins using the small peptides ATN-161 and Cilengitide, respectfully, has been shown to reduce viral infectivity in vivo and attenuate vascular inflammation (Amruta et al., 2021; Nader et al., 2021; Robles et al., 2022). We, therefore, propose an urgent examination into the therapeutic potential of integrins as therapeutics targets for SARS-CoV-2 (Figure 1).

Recommended Citation

Gressett TE, Nader D, Robles JP, Buranda T, Kerrigan SW, Bix G. Integrins as Therapeutic Targets for SARS-CoV-2. Front Cell Infect Microbiol. 2022 Apr 29;12:892323. doi: 10.3389/fcimb.2022.892323. PMID: 35619646; PMCID: PMC9128570.