In silico structural elucidation of the rabies RNA-dependent RNA polymerase (RdRp) and human epidermal growth factor receptor tyrosine kinase towards the Identification of Potential Inhibitors

Name: Duangnapa Kiriwan

LCSH: Kasetsart University -- Theses. M.S. (Genetic Engineering and Bioinformatics) 2020

Classification :.LCCS: QR415

LCSH: Kasetsart University. -- Interdisciplinary Graduate Program -- Theses

LCSH: Rabies virus

LCSH: Rhabdoviruses

LCSH: Ribosomes

LCSH: Nucleoproteins

Abstract: The Rabies virus (RABV) is a non-segmented, negative single-stranded RNA virus which causes acute infection of the central nervous system in humans. Once symptoms appear, the result is nearly always death. Nowadays, only post-exposure prophylaxis (PEP), is the immediate treatment of a bite after exposure. Previous studies have identified viral RNA dependent RNA polymerase (RdRp) as a potential drug target due to its significant role in viral replication and transcription. Herein the homology modeling of RABIES-RdRp was used to study the virus using molecular dynamics simulation and performance of virtual screening to identify potential inhibitors against RdRp. Here, five possible ligand molecules after a virtual screening of the 2,045 NCI Diversity Set III library were identified. The Z01690699 ligand molecule is suggested to be a potential inhibitor for RNA polymerase since it has a minimum molecular dynamics simulations (MDs) energy score in comparison to other molecules molecular dynamics simulation was used to elucidate the interaction with The RdRp showing that Z01690699 has stable hydrogen bonds and hydrophobic interactions with the catalytic site residue. Our study identified an important ligand for development in a remedial approach for the treatment of rabies infection, Epidermal growth factor receptor (EGFR) has been widely to be an expression or mutated in various tumors. Targeted inhibition of EGFR activity has known as a rational target for cancer therapy. In this study, 8000 tripeptides from the in-house database were virtually screened against the EGFR-TK using the GOLD program. Based on molecular docking results presents five potential hits: WFF, YWF, FWF, FWW, and WFW that indicate high binding energies that range between 43.44-43.78 kcal/mol. The top 5 tripeptides were identified as candidate small-molecular EGFR-TK complex inhibitors and determined by using EGFR-TK inhibition. Only one tripeptide, WFF was identified with IC50 value against EGFR-TK comparable erlotinib: 0.619 µM. Furthermore, the relative binding free energies calculated by MM/PBSA were comparable to the inhibition experiment in that WFF was -20.34 ± 1.61 KJ/mol. Binding energy calculation support that the EGFR-TK/inhibitor interactions were dominated with key residues around the binding pocket by van der Waals and electrostatic contributions. Our results suggest that this tripeptide could be developed as anticancer drugs in the future

Kasetsart University. Office of the University Library

Address: Bangkok

Email: tdckulib@ku.ac.th

Name: Kiattawee Choowongkomon

Role: Thesis Advisor

Name: Napat Sonttawee

Role: Thesis Co-Advisor

Created: 2020

Modified: 2026-06-15

Issued: 2026-06-15

วิทยานิพนธ์/Thesis

วิทยานิพนธ์/Thesis

application/pdf

URL: https://kasetsart.idm.oclc.org/login?url=https://www.lib.ku.ac.th/KUthesis/2563/duangnapa-kir-all.pdf

CallNumber: QR415.D82

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Genetic Engineering

Grantor: Kasetsart University

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