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.
Full text not available from this repository.Abstract
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
| Item Type: | Article |
|---|---|
| Funders: | University of Malaya Small Research Fund (Grant No: BK016-2018), MAKNA Research Grant (Grant No: PV026-2018), Malaysia Ministry of Education |
| Uncontrolled Keywords: | Dengue envelope inhibitors; Antiviral peptides; Molecular dynamics; Molecular docking |
| Subjects: | Q Science > QA Mathematics > QA75 Electronic computers. Computer science Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Medicine Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 20 Oct 2023 04:22 |
| Last Modified: | 20 Oct 2023 04:22 |
| URI: | http://eprints.um.edu.my/id/eprint/41836 |
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