Assessing the therapeutic potential of agomelatine, ramelteon, and melatonin against SARS-CoV-2

被引:7
作者
Yadalam, Pradeep Kumar [1 ]
Balaji, Thodur Madapusi [2 ]
Varadarajan, Saranya [3 ]
Alzahrani, Khalid J. [4 ]
Al-Ghamdi, Mohammad S. [4 ]
Baeshen, Hosam Ali [5 ]
Alfarhan, Mohammed Farhan A. [6 ]
Khurshid, Zohaib [7 ]
Bhandi, Shilpa [8 ]
Jagannathan, Raghunathan [2 ]
Patil, Vikrant R. [9 ]
Raj, A. Thirumal [3 ]
Ratnayake, Jithendra [10 ]
Patil, Shankargouda [11 ]
机构
[1] Saveetha Univ, Saveetha Dent Coll & Hosp, Saveetha Inst Med & Tech Sci, Dept Periodont, Chennai, Tamil Nadu, India
[2] Tagore Dent Coll & Hosp, Dept Periodontol, Chennai, Tamil Nadu, India
[3] Sri Venkateswara Dent Coll & Hosp, Dept Oral Pathol & Microbiol, Chennai, Tamil Nadu, India
[4] Taif Univ, Coll Appl Med Sci, Dept Clin Labs Sci, Taif, Saudi Arabia
[5] King Abdulaziz Univ, Fac Dent, Dept Orthodont, Jeddah, Saudi Arabia
[6] King Faisal Univ, Coll Med, Dept Surg, Al Hasa, Saudi Arabia
[7] King Faisal Univ, Coll Dent, Dept Prosthodont & Dent Implantol, Al Hasa, Saudi Arabia
[8] Jazan Univ, Dept Restorat Dent Sci, Coll Dent, Jazan, Saudi Arabia
[9] Biogenre Private Ltd, Pune, Maharashtra, India
[10] Univ Otago, Fac Dent, Dept Oral Sci, 310 Great King St, Dunedin 9016, New Zealand
[11] Jazan Univ, Coll Dent, Dept Maxillofacial Surg & Diagnost Sci, Div Oral Pathol, Jazan, Saudi Arabia
关键词
ACE; 2; In silico; Melatonin; SARS-CoV-2; Spike protein; ACE2; EXPRESSION; RECEPTOR;
D O I
10.1016/j.sjbs.2022.01.049
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: The SARS-Cov-2(severe acute respiratory syndrome coronavirus 2) infection affecting human populations worldwide is now a very concerning issue considering the morbidity and mortality rates. Despite several measures followed by the medical fraternity and general public, there is no resolution. Therapeutic measures to tackle the infection have been based on researching new designer drug molecules that could prevent viral entry into the human host. Melatonin has been tried as an adjuvant in the management of COVID 19(coronavirus disease) illness but its specific antiviral role has not been investigated.Objectives: The objectives of the present study were to conduct an in-silico analysis to investigate if melatonin and related drugs namely ramelteon and agomelatine could be used as antiviral agents in SARS-CoV-2 infection based on their binding to the SARS-CoV-2 receptor binding site (RBD) and Angiotensin-converting enzyme 2 (ACE 2).Methods: For docking studies (Pdb Id 1M0J), the SARS-CoV-2 spike protein receptor-binding domain (RBD) crystal structure which was ACE2 cell receptor bounded was employed. From the PubChem database, the three-dimensional configuration of the ligands melatonin, ramelteon, and agomelatine was retrieved, and conceptual density functional theory (CDFT) was performed to determine molecular descriptors. Charges were added and optimized with the universal force field to prepare the ligands for the process of docking. For facilitation of readability by the AutoDock software conversion to PDBQT(Protein Data Bank, Partial Charge (Q), & Atom Type (T)) format was performed. AutoDock version 4.2.6 docking program and AutoDock Tools (ADT) version 1.5.6 were used for molecular docking. Desmond, a Package of Schrodinger LLC was used to simulate molecular dynamics for hundred nanoseconds using.Results: Data from the present study reveal that melatonin, ramelteon, and agomelatine demonstrate significant binding with SARS-CoV-2 RBD and ACE 2 demonstrating the fact that they can strongly prevent viral entry into the host cells through dual binding effects. However, Ramelteon was found to be the most superior amongst the 3 drugs analyzed in its antiviral properties against SARS-CoV-2. Conclusion: Results advocate further research in exploring the potential therapeutic applications of melatonin, ramelteon, and agomelatine for the management of SARS-CoV-2 infection.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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收藏
页码:3140 / 3150
页数:11
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