Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents

Frontiers in Microbiology

Microbiology

Javiera Baeza¹  Suresh V. Chinni²  Ghadeer M. Albadrani³  Gobinath Ramachawolran⁴  Fayez M. Saleh⁵  Sajjat Mahmood⁶  Nobendu Mukerjee⁷  Mohamed M. Abdel-Daim⁸  Md. Rezaul Islam⁹  Shopnil Akash⁹  Amany A. Sayed^1,10  Vinibha Rajakumari^1,11  Vetriselvan Subramaniyan^1,12  Gaurav Gupta^1,13 

[1] Center for Bioinformatics and Molecular Simulation, Universidad de Talca, Talca, Chile;Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD), Universidad de Chile, Santiago, Chile;Department of Biochemistry, Faculty of Medicine, Bioscience, and Nursing, MAHSA University, Selangor, Malaysia;Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India;Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia;Department of Foundation, RCSI & UCD Malaysia Campus, Pulau Pinang, Malaysia;Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia;Department of Microbiology, Jagannath University, Dhaka, Bangladesh;Department of Microbiology, West Bengal State University, West Bengal, Kolkata, India;Department of Health Sciences, Novel Global Community Educational Foundation, Hebersham, NSW, Australia;Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia;Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt;Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International, University, Dhaka, Bangladesh;Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt;Faculty of Foundation, MAHSA University, Selangor, Malaysia;Pharmacology Unit, Jeffrey Cheah School of Medicine and Health Sciences, MONASH University, Jalan Lagoon Selatan, Bandar Sunway, Selangor, Malaysia;Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospital, Saveetha University, Chennai, Tamil Nadu, India;School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India;Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India;

关键词: Lassa fever virus;    emerging viral infections;    drug discovery;    ADMET;    molecular docking;    molecular dynamics simulation;    evodiamine;   

DOI  :  10.3389/fmicb.2023.1206872

 received in 2023-04-16, accepted in 2023-06-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

【 授权许可】

Unknown   
Copyright © 2023 Akash, Baeza, Mahmood, Mukerjee, Subramaniyan, Islam, Gupta, Rajakumari, Chinni, Ramachawolran, Saleh, Albadrani, Sayed and Abdel-Daim.

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