HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation

The coronavirus (COVID-19) pandemic is still spreading all over the world. As reported, angiotensin-converting enzyme-2 (ACE2) is a receptor of SARS-CoV-2 spike protein that initializes viral entry into host cells. Previously, the human defensin 5 (HD5) has been experimentally confirmed to be functi...

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Autores principales: Li, Daixi, Chen, Peiqin, Shi, Ting, Mehmood, Aamir, Qiu, Jingfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Original Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346780/
https://www.ncbi.nlm.nih.gov/pubmed/34363600
http://dx.doi.org/10.1007/s12539-021-00462-3
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author Li, Daixi
Chen, Peiqin
Shi, Ting
Mehmood, Aamir
Qiu, Jingfei
author_facet Li, Daixi
Chen, Peiqin
Shi, Ting
Mehmood, Aamir
Qiu, Jingfei
author_sort Li, Daixi
collection PubMed
description The coronavirus (COVID-19) pandemic is still spreading all over the world. As reported, angiotensin-converting enzyme-2 (ACE2) is a receptor of SARS-CoV-2 spike protein that initializes viral entry into host cells. Previously, the human defensin 5 (HD5) has been experimentally confirmed to be functional against the SARS-CoV-2. The present study proposes a human cathelicidin known as LL37 that strongly binds to the carboxypeptidase domain of human ACE2 compared to HD5. Therefore, LL37 bears a great potential to be tested as an anti-SARS-CoVD-2 peptide. We investigated the molecular interactions formed between the LL37 and ACE2 as well as HD5 and ACE2 tailed by their thermodynamic stability. The MM-PBSA and free energy landscape analysis outcomes confirmed its possible inhibitory effect against the SARS-CoV-2. The results obtained here could help propose a promising therapeutic strategy against the havoc caused by SARS-CoV-2 infections. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12539-021-00462-3.
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spelling pubmed-83467802021-08-09 HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation Li, Daixi Chen, Peiqin Shi, Ting Mehmood, Aamir Qiu, Jingfei Interdiscip Sci Original Research Article The coronavirus (COVID-19) pandemic is still spreading all over the world. As reported, angiotensin-converting enzyme-2 (ACE2) is a receptor of SARS-CoV-2 spike protein that initializes viral entry into host cells. Previously, the human defensin 5 (HD5) has been experimentally confirmed to be functional against the SARS-CoV-2. The present study proposes a human cathelicidin known as LL37 that strongly binds to the carboxypeptidase domain of human ACE2 compared to HD5. Therefore, LL37 bears a great potential to be tested as an anti-SARS-CoVD-2 peptide. We investigated the molecular interactions formed between the LL37 and ACE2 as well as HD5 and ACE2 tailed by their thermodynamic stability. The MM-PBSA and free energy landscape analysis outcomes confirmed its possible inhibitory effect against the SARS-CoV-2. The results obtained here could help propose a promising therapeutic strategy against the havoc caused by SARS-CoV-2 infections. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12539-021-00462-3. Springer Singapore 2021-08-07 2021 /pmc/articles/PMC8346780/ /pubmed/34363600 http://dx.doi.org/10.1007/s12539-021-00462-3 Text en © International Association of Scientists in the Interdisciplinary Areas 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Research Article
Li, Daixi
Chen, Peiqin
Shi, Ting
Mehmood, Aamir
Qiu, Jingfei
HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation
title HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation
title_full HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation
title_fullStr HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation
title_full_unstemmed HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation
title_short HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation
title_sort hd5 and ll-37 inhibit sars-cov and sars-cov-2 binding to human ace2 by molecular simulation
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346780/
https://www.ncbi.nlm.nih.gov/pubmed/34363600
http://dx.doi.org/10.1007/s12539-021-00462-3
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