ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics

The COVID-19 pandemic that began in late 2019 continues with new challenges arising due to antigenic drift as well as individuals who cannot or choose not to take the vaccine. There is therefore an urgent need for additional therapies that complement vaccines and approved therapies such as antibodie...

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Autores principales:	Lennox Chitsike, John Krstenansky, Penelope J. Duerksen-Hughes
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d6e879b16c5548e1968b728e0cc242cb
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spelling	oai:doaj.org-article:d6e879b16c5548e1968b728e0cc242cb2021-11-15T01:19:42ZACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics2633-469010.1155/2021/1828792https://doaj.org/article/d6e879b16c5548e1968b728e0cc242cb2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/1828792https://doaj.org/toc/2633-4690The COVID-19 pandemic that began in late 2019 continues with new challenges arising due to antigenic drift as well as individuals who cannot or choose not to take the vaccine. There is therefore an urgent need for additional therapies that complement vaccines and approved therapies such as antibodies in the fight to end or slow down the pandemic. SARS-CoV-2 initiates invasion of the human target cell through direct contact between the receptor-binding domain of its Spike protein and its cellular receptor, angiotensin-converting enzyme-2 (ACE2). The ACE2 and S1 RBD interaction, therefore, represents an attractive therapeutic intervention to prevent viral entry and spread. In this study, we developed a proximity-based AlphaScreen™ assay that can be utilized to quickly and efficiently screen for inhibitors that perturb the ACE2 : S1 RBD interaction. We then designed several peptides candidates from motifs in ACE2 and S1 RBD that play critical roles in the interaction, with and without modifications to the native sequences. We also assessed the possibility of reprofiling of candidate small molecules that previously have been shown to interfere with the viral entry of SARS-CoV. Using our optimized AlphaScreen™ assay, we evaluated the activity and specificity of these peptides and small molecules in inhibiting the binding of ACE2 : S1 RBD. This screen identified cepharanthine as a promising candidate for development as a SARS-CoV-2 entry inhibitor.Lennox ChitsikeJohn KrstenanskyPenelope J. Duerksen-HughesHindawi LimitedarticleTherapeutics. PharmacologyRM1-950ENAdvances in Pharmacological and Pharmaceutical Sciences, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Lennox Chitsike John Krstenansky Penelope J. Duerksen-Hughes ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics
description	The COVID-19 pandemic that began in late 2019 continues with new challenges arising due to antigenic drift as well as individuals who cannot or choose not to take the vaccine. There is therefore an urgent need for additional therapies that complement vaccines and approved therapies such as antibodies in the fight to end or slow down the pandemic. SARS-CoV-2 initiates invasion of the human target cell through direct contact between the receptor-binding domain of its Spike protein and its cellular receptor, angiotensin-converting enzyme-2 (ACE2). The ACE2 and S1 RBD interaction, therefore, represents an attractive therapeutic intervention to prevent viral entry and spread. In this study, we developed a proximity-based AlphaScreen™ assay that can be utilized to quickly and efficiently screen for inhibitors that perturb the ACE2 : S1 RBD interaction. We then designed several peptides candidates from motifs in ACE2 and S1 RBD that play critical roles in the interaction, with and without modifications to the native sequences. We also assessed the possibility of reprofiling of candidate small molecules that previously have been shown to interfere with the viral entry of SARS-CoV. Using our optimized AlphaScreen™ assay, we evaluated the activity and specificity of these peptides and small molecules in inhibiting the binding of ACE2 : S1 RBD. This screen identified cepharanthine as a promising candidate for development as a SARS-CoV-2 entry inhibitor.
format	article
author	Lennox Chitsike John Krstenansky Penelope J. Duerksen-Hughes
author_facet	Lennox Chitsike John Krstenansky Penelope J. Duerksen-Hughes
author_sort	Lennox Chitsike
title	ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics
title_short	ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics
title_full	ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics
title_fullStr	ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics
title_full_unstemmed	ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics
title_sort	ace2 : s1 rbd interaction-targeted peptides and small molecules as potential covid-19 therapeutics
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/d6e879b16c5548e1968b728e0cc242cb
work_keys_str_mv	AT lennoxchitsike ace2s1rbdinteractiontargetedpeptidesandsmallmoleculesaspotentialcovid19therapeutics AT johnkrstenansky ace2s1rbdinteractiontargetedpeptidesandsmallmoleculesaspotentialcovid19therapeutics AT penelopejduerksenhughes ace2s1rbdinteractiontargetedpeptidesandsmallmoleculesaspotentialcovid19therapeutics
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ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics

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