An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms

Yi Wei Chan; Choo Hock Tan; Choon Han Heh; Kae Yi Tan

doi:10.3389/fphar.2023.1143437

An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms

Front Pharmacol. 2023 Apr 10:14:1143437. doi: 10.3389/fphar.2023.1143437. eCollection 2023.

Authors

Yi Wei Chan¹, Choo Hock Tan², Choon Han Heh³, Kae Yi Tan¹

Affiliations

¹ Protein and Interactomics Laboratory, Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
² Venom Research and Toxicology Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Malaya, Kuala Lumpur, Malaysia.

Abstract

Introduction: Most elapid snakes produce venoms that contain alpha-neurotoxins (α-NTXs), which are proteins that cause post-synaptic blockade and paralysis in snakebite envenoming. However, existing elapid antivenoms are known for their low potency in neutralizing the neurotoxic activity of α-NTXs, while the immunological basis has not been elucidated. Methods: In this study, a structure-based major histocompatibility complex II (MHCII) epitope predictor of horse (Equus caballus), complemented with DM-editing determinant screening algorithm was adopted to assess the immunogenicity of α-NTXs in the venoms of major Asiatic elapids (Naja kaouthia, Ophiophagus hannah, Laticauda colubrina, Hydrophis schistosus, Hydrophis curtus). Results: The scoring metric M₂R, representing the relative immunogenic performance of respective α-NTXs, showed all α-NTXs have an overall low M₂R of <0.3, and most of the predicted binders feature non-optimal P1 anchor residues. The M₂R scores correlate strongly (R² = 0.82) with the potency scores (p-score) generated based on the relative abundances of α-NTXs and the neutralization potency of commercial antivenoms. Discussion: The immunoinformatic analysis indicates that the inferior antigenicity of α-NTXs is not only due to their small molecular size but also the subpar immunogenicity affected by their amino acid composition. Structural modification with conjugation and synthetic epitope as immunogen may potentially enhance the immunogenicity for improved antivenom potency against α-NTXs of elapid snakes.

Keywords: antigenicity; antivenom efficacy; bioinformatics; immunogenicity; molecular docking; three-finger toxins.

Grants and funding

This work was supported by the Fundamental Research Grant (FRGS/1/2019/SKK08/UM/02/2) from the Ministry of Higher Education, Malaysia.