| Autor: |
Rabaan AA; Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.; Department of Public Health and Nutrition, The University of Haripur, Haripur, Pakistan., AlShehail BM; Pharmacy Practice Department, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., Halwani MA; Department of Medical Microbiology, Faculty of Medicine, Al Baha University, Saudi Arabia., Alshengeti A; Department of Pediatrics, College of Medicine, Taibah University, Al-Madinah, Saudi Arabia.; Department of Infection Prevention and Control, Prince Mohammad Bin Abdulaziz Hospital, National Guard Health Affairs, Al-Madinah, Saudi Arabia., Najim MA; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia., Garout M; Department of Community Medicine and Health Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia., Bajunaid HA; Makkah Specialized Laboratory, Fakeeh Care group, Hadda, Saudi Arabia., Alshamrani SA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia., Al Fares MA; Department of Internal Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Alissa M; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia., Alwashmi ASS; Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia. |
| Abstrakt: |
Zika virus (ZIKV) spread is considered a major public health threat by the World Health Organization (WHO). There are no vaccines or drugs available to control the infection of the Zika virus, therefore a highly effective medicinal molecule is urgently required. In this study, a computationally intensive investigation was performed to identify a potent natural compound that could inhibit the ZIKV NS5 methyltransferase. This research approach is based on target-based drug identification principles where the native inhibitor SAH (S-adenosylhomocysteine) of ZIKV NS5 methyltransferase was selected as a reference. High-throughput virtual screening and tanimoto similarity coefficient were applied to the natural compound library for ranking the potential candidates. The top five compounds were selected for interaction analysis, MD simulation, total binding free energy through MM/GBSA, and steered MD simulation. Among these compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin showed stable binding to the protein compared to the native compound, SAH. These three compounds also showed less fluctuations in RMSF in contrast to native compound. Additionally, the same interacting residues observed in SAH also made strong interactions with these three compounds. Adenosine 5'-monophosphate monohydrate and 5-Iodotubercidin had greater total binding free energies than the reference ligand. Moreover, the dissociation resistance of all three compounds was equivalent to that of the reference ligand. This study suggested binding properties of three-hit compounds that could be used to develop drugs against Zika virus infections.Communicated by Ramaswamy H. Sarma. |
