The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection

Brandon J Beddingfield; Naoki Iwanaga; Prem P Chapagain; Wenshu Zheng; Chad J Roy; Tony Y Hu; Jay K Kolls; Gregory J Bix

doi:10.1016/j.jacbts.2020.10.003

The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection

JACC Basic Transl Sci. 2021 Jan;6(1):1-8. doi: 10.1016/j.jacbts.2020.10.003. Epub 2020 Oct 16.

Authors

Brandon J Beddingfield^{1

2}, Naoki Iwanaga³, Prem P Chapagain^{4

5}, Wenshu Zheng⁶, Chad J Roy^{1

2}, Tony Y Hu⁶, Jay K Kolls³, Gregory J Bix^{7

8

9

10

11}

Affiliations

¹ Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
² Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
³ Departments of Pediatrics and Medicine, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁴ Department of Physics, Florida International University, Miami, Florida, USA.
⁵ Biomolecular Sciences Institute, Florida International University, Miami, Florida, USA.
⁶ Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁷ Clinical Neuroscience Research Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁸ Department of Neurosurgery, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁹ Department of Neurology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
¹⁰ Tulane Brain Institute, Tulane University, New Orleans, Louisiana, USA.
¹¹ Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.

Abstract

Many efforts to design and screen therapeutics for the current severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic have focused on inhibiting viral host cell entry by disrupting angiotensin-converting enzyme-2 (ACE2) binding with the SARS-CoV-2 spike protein. This work focuses on the potential to inhibit SARS-CoV-2 entry through a hypothesized α5β1 integrin-based mechanism and indicates that inhibiting the spike protein interaction with α5β1 integrin (+/- ACE2) and the interaction between α5β1 integrin and ACE2 using a novel molecule (ATN-161) represents a promising approach to treat coronavirus disease-19.

Keywords: ACE2; ACE2, angiotensin-converting enzyme 2; ATN-161; CO2, carbon dioxide; COVID-19; COVID-19, coronavirus disease-2019; DMEM, Dulbecco’s modified eagle media; ELISA, enzyme-linked immunosorbent assay; IC50, half-maximal inhibitory concentration; RBD, receptor binding domain; RGD, arginine-glycine-aspartate; SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; alpha5beta1 integrin; hACE2, human angiotensin-converting enzyme 2; host-cell entry; qPCR, quantitative polymerase chain reaction; receptor binding domain; therapeutic; viral spike protein.

Grants and funding

P51 OD011104/OD/NIH HHS/United States