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

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...

Full description

Saved in:

Bibliographic Details
Published in:	Neurogenetics Vol. 25; no. 3; pp. 263 - 275
Main Authors:	Ojo, Taiwo Ooreoluwa, Elegbeleye, Oluwabamise Emmanuel, Bolaji, Olawale Quadri, Adelusi, Temitope Isaac, Oladipo, Elijah Kolawole, Olawuyi, Matthew Oluwaseun, Afolayan, Bukola Oluwafunmilayo, Oyaronbi, Adegboye Oyewole, Ogunjobi, Taiwo Temitope, Oyewole, Moyosoluwa Precious, Folorunso, Kolade Pelumi, Ogunlana, Abdeen Tunde
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2024 Springer Nature B.V
Subjects:	Amino acid sequence Antigens Argonaute 2 protein Central nervous system Computational neuroscience Conserved sequence Demyelination EBNA-1 protein Epstein-Barr virus Epstein-Barr Virus Infections - complications Epstein-Barr Virus Infections - therapy Epstein-Barr Virus Nuclear Antigens - genetics Exploration Herpesvirus 4, Human - genetics Human Genetics Humans Immune response Immune system Immunoglobulin G Medicine Medicine & Public Health Molecular Medicine mRNA Multiple sclerosis Multiple Sclerosis - genetics Multiple Sclerosis - therapy Myelin Neurology Neurosciences Protein structure RNA, Small Interfering - genetics RNA, Small Interfering - therapeutic use Secondary structure siRNA Symptom management EBNA-1 Multiple sclerosis siRNA Epstein Barr virus Auto-immune Computational
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. Graphical Abstract
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1364-6753 1364-6745 1364-6753
DOI:	10.1007/s10048-024-00764-w