Staff View: Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells

Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells

Dengue virus (DV) infection is one of the main public health concerns, affecting approximately 390 million people worldwide, as reported by the World Health Organization. Yet, there is no antiviral treatment for DV infection. Therefore, the development of potent and nontoxic anti-DV, as a complement...

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Main Authors:	Arumugam, Aathe Cangaree, Agharbaoui, Fatima Ezzahra, Khazali, Ahmad Suhail, Yusof, Rohana, Abd Rahman, Noorsaadah, Ahmad Fuaad, Abdullah Al Hadi
Format:	Article
Published:	Taylor & Francis 2022
Subjects:	QA75 Electronic computers. Computer science QH301 Biology
Online Access:	http://eprints.um.edu.my/41836/
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spelling	my.um.eprints.418362023-10-20T04:22:13Z http://eprints.um.edu.my/41836/ Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells Arumugam, Aathe Cangaree Agharbaoui, Fatima Ezzahra Khazali, Ahmad Suhail Yusof, Rohana Abd Rahman, Noorsaadah Ahmad Fuaad, Abdullah Al Hadi QA75 Electronic computers. Computer science QH301 Biology Dengue virus (DV) infection is one of the main public health concerns, affecting approximately 390 million people worldwide, as reported by the World Health Organization. Yet, there is no antiviral treatment for DV infection. Therefore, the development of potent and nontoxic anti-DV, as a complement for the existing treatment strategies, is urgently needed. Herein, we investigate a series of small peptides inhibitors of DV antiviral activity targeting the entry process as the promising strategy to block DV infection. The peptides were designed based on our previously reported peptide sequence, DN58opt (TWWCFYFCRRHHPFWFFYRHN), to identify minimal effective inhibitory sequence through molecular docking and dynamics studies. The in silico designed peptides were synthesized using conventional Fmoc solid-phase peptide synthesis chemistry, purified by RP-HPLC and characterized using LCMS. Later, they were screened for their antiviral activity. One of the peptides, AC 001, was able to reduce about 40% of DV plaque formation. This observation correlates well with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) analysis - AC 001 showed the most favorable binding affinity through 60 ns simulations. Pairwise residue decomposition analysis has revealed four key residues that contributed to the binding of these peptides into the DV2 E protein pocket. This work identifies the minimal peptide sequence required to inhibit DV replication and explains the behavior observed on an atomic level using computational study. Communicated by Ramaswamy H. Sarma Taylor & Francis 2022-06-28 Article PeerReviewed Arumugam, Aathe Cangaree and Agharbaoui, Fatima Ezzahra and Khazali, Ahmad Suhail and Yusof, Rohana and Abd Rahman, Noorsaadah and Ahmad Fuaad, Abdullah Al Hadi (2022) Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells. Journal of Biomolecular Structure and Dynamics, 40 (11). pp. 5026-5035. ISSN 0739-1102, DOI https://doi.org/10.1080/07391102.2020.1866074 <https://doi.org/10.1080/07391102.2020.1866074>. 10.1080/07391102.2020.1866074
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	QA75 Electronic computers. Computer science QH301 Biology
spellingShingle	QA75 Electronic computers. Computer science QH301 Biology Arumugam, Aathe Cangaree Agharbaoui, Fatima Ezzahra Khazali, Ahmad Suhail Yusof, Rohana Abd Rahman, Noorsaadah Ahmad Fuaad, Abdullah Al Hadi Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells
description	Dengue virus (DV) infection is one of the main public health concerns, affecting approximately 390 million people worldwide, as reported by the World Health Organization. Yet, there is no antiviral treatment for DV infection. Therefore, the development of potent and nontoxic anti-DV, as a complement for the existing treatment strategies, is urgently needed. Herein, we investigate a series of small peptides inhibitors of DV antiviral activity targeting the entry process as the promising strategy to block DV infection. The peptides were designed based on our previously reported peptide sequence, DN58opt (TWWCFYFCRRHHPFWFFYRHN), to identify minimal effective inhibitory sequence through molecular docking and dynamics studies. The in silico designed peptides were synthesized using conventional Fmoc solid-phase peptide synthesis chemistry, purified by RP-HPLC and characterized using LCMS. Later, they were screened for their antiviral activity. One of the peptides, AC 001, was able to reduce about 40% of DV plaque formation. This observation correlates well with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) analysis - AC 001 showed the most favorable binding affinity through 60 ns simulations. Pairwise residue decomposition analysis has revealed four key residues that contributed to the binding of these peptides into the DV2 E protein pocket. This work identifies the minimal peptide sequence required to inhibit DV replication and explains the behavior observed on an atomic level using computational study. Communicated by Ramaswamy H. Sarma
format	Article
author	Arumugam, Aathe Cangaree Agharbaoui, Fatima Ezzahra Khazali, Ahmad Suhail Yusof, Rohana Abd Rahman, Noorsaadah Ahmad Fuaad, Abdullah Al Hadi
author_facet	Arumugam, Aathe Cangaree Agharbaoui, Fatima Ezzahra Khazali, Ahmad Suhail Yusof, Rohana Abd Rahman, Noorsaadah Ahmad Fuaad, Abdullah Al Hadi
author_sort	Arumugam, Aathe Cangaree
title	Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells
title_short	Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells
title_full	Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells
title_fullStr	Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells
title_full_unstemmed	Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells
title_sort	computational-aided design: minimal peptide sequence to block dengue virus transmission into cells
publisher	Taylor & Francis
publishDate	2022
url	http://eprints.um.edu.my/41836/
_version_	1781704562468454400
score	13.211869

Computational-aided design: Minimal peptide sequence to block dengue virus transmission into cells

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