Hitting Epstein Barr virus where it hurts: computational methods exploration for siRNA therapy in alleviating Epstein Barr virus-induced multiple sclerosis.

Autor: Ojo TO; Computational Molecular Biology and Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.; Division of Vaccine Design and Development, Helix Biogen Institute, Ogbomoso, Oyo State, 210214, Nigeria., Elegbeleye OE; Computational Molecular Biology and Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria., Bolaji OQ; Computational Molecular Biology and Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria., Adelusi TI; Computational Molecular Biology and Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.; Department of Surgery, School of Medicine, University of Connecticut Health, Farmington Ave, Connecticut, 06030, United States of America., Oladipo EK; Division of Vaccine Design and Development, Helix Biogen Institute, Ogbomoso, Oyo State, 210214, Nigeria.; Department of Microbiology, Laboratory of Molecular Biology, Immunology and Bioinformatics, Adeleke University, Ede, Osun State, 232104, Nigeria., Olawuyi MO; Computational Molecular Biology and Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria., Afolayan BO; Computational Molecular Biology and Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria., Oyaronbi AO; Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria., Ogunjobi TT; Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria., Oyewole MP; Biochemistry program, Bowen University, Iwo, Osun State, Nigeria., Folorunso KP; Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria., Ogunlana AT; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo State, 200005, Nigeria. atogunlana@student.lautech.edu.ng.
Jazyk: angličtina
Zdroj: Neurogenetics [Neurogenetics] 2024 Jul; Vol. 25 (3), pp. 263-275. Date of Electronic Publication: 2024 May 29.
DOI: 10.1007/s10048-024-00764-w
Abstrakt: Multiple sclerosis (MS), an intricate neurological disorder, continues to challenge our understanding of the pivotal interplay between the immune system and the central nervous system (CNS). This condition arises from the immune system's misdirected attack on nerve fiber protection, known as myelin sheath, alongside nerve fibers themselves. This enigmatic condition, characterized by demyelination and varied clinical manifestations, prompts exploration into its multifaceted etiology and potential therapeutic avenues. Research has revealed a potential connection between Epstein Barr virus (EBV), specifically Epstein Barr Nuclear Antigen 1 (EBNA-1), and MS. The immune response to EBNA-1 antigen triggers the production of anti-EBNA-1 molecules, including IgG that identify a similar amino acid sequence to EBNA-1 in myelin, inadvertently targeting myelin sheath and contributing to MS progression. Currently, no treatment exists for EBNA-1-induced MS apart from symptom management. Addressing this, a novel potential therapeutic avenue utilizing small interference RNAs (siRNA) has been designed. By targeting the conserved EBNA-1 gene sequences in EBV types 1 and 2, five potential siRNAs were identified in our analysis. Thorough evaluations encompassing off-target binding, thermodynamics and secondary structure elucidation, efficacy prediction, siRNA-mRNA sequence binding affinity exploration, melting temperature, and docking of siRNAs with human argonaute protein 2 (AGO2) were conducted to elucidate the siRNAs efficiency. These designed siRNA molecules harnessed promising silencing activity in the EBNA-1 gene encoding the EBNA-1 antigen protein and thus have the potential to mitigate the severity of this dangerous virus.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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