Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)

Abstract: Enterovirus 71 (EV-A71) is one of the predominant etiological agents of hand, foot and mouth disease (HMFD), which can cause severe central nervous system infections in young children. There is no clinically approved vaccine or antiviral agent against HFMD. The SP40 peptide, derived from t...

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Main Authors:	Masomian, Malihe , Lalani, S., Poh, Chit Laa *
Format:	Article
Language:	English
Published:	MDPI 2021
Subjects:	QR355 Virology
Online Access:	http://eprints.sunway.edu.my/1883/ http://eprints.sunway.edu.my/1883/1/Malihe%20Masomian%20Molecular%20Docking%20Molecules-26-06576.pdf

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author	Masomian, Malihe * Lalani, S.* Poh, Chit Laa *
author_facet	Masomian, Malihe * Lalani, S.* Poh, Chit Laa *
author_sort	Masomian, Malihe *
building	SU Institutional Repository
collection	Online Access
description	Abstract: Enterovirus 71 (EV-A71) is one of the predominant etiological agents of hand, foot and mouth disease (HMFD), which can cause severe central nervous system infections in young children. There is no clinically approved vaccine or antiviral agent against HFMD. The SP40 peptide, derived from the VP1 capsid of EV-A71, was reported to be a promising antiviral peptide that targeted the host receptor(s) involved in viral attachment or entry. So far, the mechanism of action of SP40 peptide is unknown. In this study, interactions between ten reported cell receptors of EV-A71 and the antiviral SP40 peptide were evaluated through molecular docking simulations, followed by in vitro receptor blocking with specific antibodies. The preferable binding region of each receptor to SP40 was predicted by global docking using HPEPDOCK and the cell receptor-SP40 peptide complexes were refined using FlexPepDock. Local molecular docking using GOLD (Genetic Optimization for Ligand Docking) showed that the SP40 peptide had the highest binding score to nucleolin followed by annexin A2, SCARB2 and human tryptophanyl-tRNA synthetase. The average Gold-Score for 5 top-scoring models of human cyclophilin, fibronectin, human galectin, DC-SIGN and vimentin were almost similar. Analysis of the nucleolin-SP40 peptide complex showed that SP40 peptide binds to the RNA binding domains (RBDs) of nucleolin. Furthermore, receptor blocking by specific monoclonal antibody was performed for seven cell receptors of EV-A71 and the results showed that the blocking of nucleolin by anti-nucleolin alone conferred a 93% reduction in viral infectivity. Maximum viral inhibition (99.5%) occurred when SCARB2 was concurrently blocked with anti-SCARB2 and the SP40 peptide. This is the first report to reveal the mechanism of action of SP40 peptide in silico through molecular docking analysis. This study provides information on the possible binding site of SP40 peptide to EV-A71 cellular receptors. Such information could be useful to further validate the interaction of the SP40 peptide with nucleolin by site-directed mutagenesis of the nucleolin binding site.
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format	Article
id	sunway-1883
institution	Sunway University
institution_category	Local University
language	English
last_indexed	2025-11-14T21:18:50Z
publishDate	2021
publisher	MDPI
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spelling	sunway-18832021-12-06T02:53:00Z http://eprints.sunway.edu.my/1883/ Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71) Masomian, Malihe * Lalani, S.* Poh, Chit Laa * QR355 Virology Abstract: Enterovirus 71 (EV-A71) is one of the predominant etiological agents of hand, foot and mouth disease (HMFD), which can cause severe central nervous system infections in young children. There is no clinically approved vaccine or antiviral agent against HFMD. The SP40 peptide, derived from the VP1 capsid of EV-A71, was reported to be a promising antiviral peptide that targeted the host receptor(s) involved in viral attachment or entry. So far, the mechanism of action of SP40 peptide is unknown. In this study, interactions between ten reported cell receptors of EV-A71 and the antiviral SP40 peptide were evaluated through molecular docking simulations, followed by in vitro receptor blocking with specific antibodies. The preferable binding region of each receptor to SP40 was predicted by global docking using HPEPDOCK and the cell receptor-SP40 peptide complexes were refined using FlexPepDock. Local molecular docking using GOLD (Genetic Optimization for Ligand Docking) showed that the SP40 peptide had the highest binding score to nucleolin followed by annexin A2, SCARB2 and human tryptophanyl-tRNA synthetase. The average Gold-Score for 5 top-scoring models of human cyclophilin, fibronectin, human galectin, DC-SIGN and vimentin were almost similar. Analysis of the nucleolin-SP40 peptide complex showed that SP40 peptide binds to the RNA binding domains (RBDs) of nucleolin. Furthermore, receptor blocking by specific monoclonal antibody was performed for seven cell receptors of EV-A71 and the results showed that the blocking of nucleolin by anti-nucleolin alone conferred a 93% reduction in viral infectivity. Maximum viral inhibition (99.5%) occurred when SCARB2 was concurrently blocked with anti-SCARB2 and the SP40 peptide. This is the first report to reveal the mechanism of action of SP40 peptide in silico through molecular docking analysis. This study provides information on the possible binding site of SP40 peptide to EV-A71 cellular receptors. Such information could be useful to further validate the interaction of the SP40 peptide with nucleolin by site-directed mutagenesis of the nucleolin binding site. MDPI 2021-10 Article PeerReviewed text en cc_by_nc_4 http://eprints.sunway.edu.my/1883/1/Malihe%20Masomian%20Molecular%20Docking%20Molecules-26-06576.pdf Masomian, Malihe * and Lalani, S.* and Poh, Chit Laa * (2021) Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71). Molecules, 26 (21). p. 6576. ISSN 1420-3049 https://www.mdpi.com/1420-3049/26/21/6576 doi:10.3390/molecules26216576
spellingShingle	QR355 Virology Masomian, Malihe * Lalani, S.* Poh, Chit Laa * Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)
title	Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)
title_full	Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)
title_fullStr	Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)
title_full_unstemmed	Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)
title_short	Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)
title_sort	molecular docking of sp40 peptide towards cellular receptors for enterovirus 71 (ev-a71)
topic	QR355 Virology
url	http://eprints.sunway.edu.my/1883/ http://eprints.sunway.edu.my/1883/ http://eprints.sunway.edu.my/1883/ http://eprints.sunway.edu.my/1883/1/Malihe%20Masomian%20Molecular%20Docking%20Molecules-26-06576.pdf

Molecular docking of SP40 peptide towards cellular receptors for enterovirus 71 (EV-A71)

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