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

Abstract

Many efforts to design and screen therapeutics for the current severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic have focused on inhibiting viral host cell entry by disrupting 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 COVID-19.

Integrating Integrins

“…This prior work sets the stage for the subject of this Editorial Comment, the paper by Beddingfield et al. ( 3 ) in this issue of JACC: Basic to Translational Science , and therefore is worth briefly reviewing. Bristow et al.…”

“…Pertinent to the Beddingfield et al. ( 3 ) paper is that Bristow et al. ( 2 ) keyed in on prior work on cellular receptors termed integrins .…”

“…Before discussing the paper by Beddingfield et al. ( 3 ), we must understand a bit about integrins and what relevance they have in the cardiovascular system, aside from a potential role in COVID-19.…”

“…In this issue of JACC: Basic to Translational Science , Beddingfield et al. ( 3 ) studied the potential role of using an integrin binding peptide, termed ATN-161, as a means to reduce or prevent SARS-CoV-2 infection. ATN-161 is derived from a domain of FN.…”

“…First, Beddingfield et al. ( 3 ) used in vitro studies to show that ATN-161 could bind the viral spike protein and could inhibit ACE2 or ACE2/α5β1 binding in a dose-dependent manner on a plastic tissue-culture plate alone. Then, using VeroE6 kidney cells of African green monkey origin that are known to express α5β1 integrin, they further showed that ATN-161 could reduce the viral load of infected cells, as well as inhibit cell damage or lysis.…”