tetano
Editor, Senior Moderator
JACC Basic Transl Sci
. 2020 Oct 16.
doi: 10.1016/j.jacbts.2020.10.003. Online ahead of print.
The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection
Brandon J Beddingfield[SUP] 1 2 [/SUP], Naoki Iwanaga[SUP] 3 [/SUP], Prem P Chapagain[SUP] 4 5 [/SUP], Wenshu Zheng[SUP] 6 [/SUP], Chad J Roy[SUP] 1 2 [/SUP], Tony Y Hu[SUP] 6 [/SUP], Jay K Kolls[SUP] 3 [/SUP], Gregory J Bix[SUP] 7 8 9 10 11 [/SUP]
Affiliations
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.
Keywords: ACE2; ACE2, angiotensin-converting enzyme II; ANOVA, analysis of variance; ATN-161; BSA, bovine serum albumin; COVID-19; COVID-19, coronavirus disease 2019; CPE, cytopathic effect; DMEM, Dulbecco’s modified eagle media; ELISA, Enzyme-Linked Immunosorbent Assay; FBS, fetal bovine serum; FN, fibronectin; HRP, horse radish peroxidase; IC50, half-maximal inhibitory concentration; KGD, lysine-glycine-aspartate; MOI, multiplicity of infection; MnCl2, Manganese Chloride; NIAID, National Institutes of Allergy and Infectious Disease; NIH, National Institutes of Health; PDB, protein data bank; RBD, receptor binding domain; RGD, arginine-glycine-aspartate; SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus; SD, standard deviation; TMB, 3,3’,5,5’-tetramethylbenzidine; Veh, vehicle; alpha5beta1 integrin; host-cell entry; qPCR, quantitative polymerase chain reaction; receptor binding domain; therapeutic; viral spike protein; α5β1, alpha5beta1.
. 2020 Oct 16.
doi: 10.1016/j.jacbts.2020.10.003. Online ahead of print.
The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection
Brandon J Beddingfield[SUP] 1 2 [/SUP], Naoki Iwanaga[SUP] 3 [/SUP], Prem P Chapagain[SUP] 4 5 [/SUP], Wenshu Zheng[SUP] 6 [/SUP], Chad J Roy[SUP] 1 2 [/SUP], Tony Y Hu[SUP] 6 [/SUP], Jay K Kolls[SUP] 3 [/SUP], Gregory J Bix[SUP] 7 8 9 10 11 [/SUP]
Affiliations
- PMID: 33102950
- PMCID: PMC7566794
- DOI: 10.1016/j.jacbts.2020.10.003
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.
Keywords: ACE2; ACE2, angiotensin-converting enzyme II; ANOVA, analysis of variance; ATN-161; BSA, bovine serum albumin; COVID-19; COVID-19, coronavirus disease 2019; CPE, cytopathic effect; DMEM, Dulbecco’s modified eagle media; ELISA, Enzyme-Linked Immunosorbent Assay; FBS, fetal bovine serum; FN, fibronectin; HRP, horse radish peroxidase; IC50, half-maximal inhibitory concentration; KGD, lysine-glycine-aspartate; MOI, multiplicity of infection; MnCl2, Manganese Chloride; NIAID, National Institutes of Allergy and Infectious Disease; NIH, National Institutes of Health; PDB, protein data bank; RBD, receptor binding domain; RGD, arginine-glycine-aspartate; SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus; SD, standard deviation; TMB, 3,3’,5,5’-tetramethylbenzidine; Veh, vehicle; alpha5beta1 integrin; host-cell entry; qPCR, quantitative polymerase chain reaction; receptor binding domain; therapeutic; viral spike protein; α5β1, alpha5beta1.