Conformational dynamics of the membrane protein of MERS-CoV in comparison with SARS-CoV-2 in ERGIC complex

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: Jan. 5, 2025

The present study explores the conformational dynamics of membrane protein Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC) complex using an all-atomistic molecular simulation approach. Significant structural changes were observed in N-terminal, C-terminal, transmembrane, and beta-sheet sandwich domains MERS-CoV protein. This also highlights similarities between SARS-CoV-2 proteins, particularly how both exhibit a distinct kink transmembrane helix caused by aromatic residue-lipid interactions. A expansion below above domain dimer was all M-proteins. site on near C-terminal end could serve as potential drug-binding site. Notably, stable helical structure identified protein, whereas proper secondary conformation not Further, exhibited stronger binding to lipid bilayer than MERS-CoV, indicating its greater stability ERGIC complex. similarity suggests feasibility employing common inhibitor against these beta-coronaviruses. Furthermore, this analysis enhances our understanding protein's interactions with proteins lipids, paving way for therapeutic developments viruses.

Language: Английский

Machine Learning-Guided Screening and Molecular Docking for Proposing Naturally Derived Drug Candidates Against MERS-CoV 3CL Protease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3047 - 3047

Published: March 26, 2025

In this study, we utilized machine learning techniques to identify potential inhibitors of the MERS-CoV 3CL protease. Among models evaluated, Random Forest (RF) algorithm exhibited highest predictive performance, achieving an accuracy 0.97, ROC-AUC score 0.98, and F1-score 0.98. Following model validation, applied it a dataset 14,194 naturally occurring compounds from PubChem. The top-ranked were subsequently subjected molecular docking, which identified Perenniporide B, Phellifuropyranone A, Terrestrol G as most promising candidates, with binding energies -9.17, -9.08, -8.71 kcal/mol, respectively. These formed strong interactions key catalytic residues, suggesting significant inhibitory against viral Furthermore, dynamics simulations confirmed their stability within active site, reinforcing viability antiviral agents. This study demonstrates effectiveness integrating modeling accelerate discovery therapeutic candidates emerging threats.

Language: Английский

MERS outbreak in Riyadh: A current concern in Saudi Arabia

Infezioni in Medicina, Journal Year: 2024, Volume and Issue: 32(2)

Published: May 30, 2024

Language: Английский