Moleküler Bağlama Yaklaşımı Kullanılarak Olası Maymun Çiçeği Salgını İçin İlaç Yeniden Konumlandırma Stratejisi

Year 2025, Volume: 13 Issue: 4, 1695 - 1718, 30.10.2025

Harun Selvitopi , Mehmet Enes Arslan , Seda Demir , Yusuf Akbaba , Murat Aydemir , Ahmet Hacımüftüoğlu , Zülküf Selvitopi , Hasan Türkez

https://doi.org/10.29130/dubited.1652693

Abstract

Bu çalışmada, maymun çiçeği virüsü için ilaç yeniden konumlandırma stratejisi, moleküler bağlama (docking) ve moleküler dinamik (MD) simülasyon yaklaşımları kullanılarak gerçekleştirilmiştir. Bu amaçla, klinik tedavide diğer hastalıklar için halihazırda onaylanmış olan olası ilaçlar taranmıştır. Potansiyel ilaç adayları, AutoDock yazılımı kullanılarak iki grupta analiz edilmiştir: 1) DNA polimeraz inhibitörleri ve 2) RNA polimeraz inhibitörleri.

Moleküler bağlama araştırmaları, maymun çiçeği enfeksiyonuna karşı etkili olabilecek toplam yedi olası ilaç adayı belirlemiştir: beşi DNA polimeraz inhibitörü ve ikisi RNA polimeraz inhibitörüdür. Ayrıca, moleküler dinamik simülasyon sonuçları, bahsedilen inhibitörlerin güçlü ilaç adayları olabileceğini doğrulamıştır. Bu aday ilaçlardan etravirine (-8,04 Kcal/mol) ve valasiklovir (-7,57 Kcal/mol), ASP347 ve ASP462 kalıntılarının aktif bölgesinde enzime karşı daha yüksek bağlanma afinitesi göstermiştir. Bunun yanı sıra, emetin dihidroklorürün, maymun çiçeği virüsünün RNA polimeraz inhibitörü olarak en güçlü ilaç adayı olduğu ve enzimin katalitik bölgesine -7,17 Kcal/mol bağlanma enerjisi ile bağlandığı gözlemlenmiştir.

Bu çalışma sonucunda, oldukça etkili bir DNA polimeraz inhibitörü olarak etravirine ve bir RNA polimeraz inhibitörü olarak emetin dihidroklorür, maymun çiçeği tedavisi için potansiyel ilaç adayları olarak önerilmektedir. Bu ilaçlar daha önce ABD Gıda ve İlaç Dairesi (FDA) tarafından diğer viral enfeksiyonlar için onaylandığından, uzun güvenlik protokollerine ve yüksek geliştirme maliyetlerine gerek kalmadan maymun çiçeği enfeksiyonu etkili bir şekilde kontrol altına alınabilir.

Keywords

monkeypox virus; , antiviral , etravirine , molecular docking , molecular dynamics simulation; , drug repurposing

Computational Identification of Potential Antiviral Agents Against Monkeypox Virus

Abstract

This study introduces a drug repurposing approach for monkeypox virus using molecular docking and molecular dynamics (MD) simulations to screen clinically approved drugs for other diseases. Potential candidates were analyzed with AutoDock software in two categories: (1) DNA polymerase inhibitors and (2) RNA polymerase inhibitors. Docking analysis identified seven promising compounds—five DNA polymerase and two RNA polymerase inhibitors—showing strong affinity toward monkeypox targets. MD simulations further confirmed their binding stability. Among them, etravirine (−8.04 kcal/mol) and valaciclovir (−7.57 kcal/mol) exhibited the highest affinity to DNA polymerase active sites at residues ASP347 and ASP462. Moreover, emetine dihydrochloride (−7.17 kcal/mol) demonstrated the strongest binding to the catalytic site of RNA polymerase. Consequently, etravirine and emetine dihydrochloride are proposed as potential therapeutics against monkeypox. Since these compounds are already approved by the U.S. Food and Drug Administration (FDA) for other viral infections, extensive safety testing and high development costs can be avoided, making this repurposing strategy an efficient and cost-effective option for managing monkeypox infection.

Keywords

Monkeypox Virus , Etravirine , Molecular Docking , Molecular Dynamics Simulation , Drug Repurposing

Ethical Statement

This study does not involve human or animal participants. All procedures followed scientific and ethical principles, and all referenced studies are appropriately cited

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