In silico selection of aptamers to cobra venom cytotoxin

Snakebite envenomation has been listed as one of the neglected tropical diseases (NTDs) by the World Health Organization (WHO) since 2017 [1]. Cytotoxin (CTX), one of the most abundant venom components, was deemed responsible for the envenomation’s local dermonecrosis. Several studies have indicated that the CTX induces cell death through different pathways, yet the molecular mechanism is inconclusive [2]. There is also limited treatment against dermonecrosis. Therefore, there is a need to search for biotherapeutics against CTX-induced dermonecrosis. In this study, we exploit the potential of tRNA-based aptamers as alternate toxin-neutralizing molecules using in silico approach. GtRNAdb database was used to identify the CTX-binding tRNA-based aptamers for the possible interacting regions with CTX [3]. The sequences of the aptamers were subjected to phylogenetic tree analysis to categorize the tRNAs into different clusters using the Clustal Omega. The tertiary structures of the consensus aptamer sequences were modeled using the RNA Composer. Later, the molecular docking of these aptamers and CTX was performed using HADDOCK web server. In addition, RING analysis was performed on each aptamer-CTX complex to determine the interacting amino acids present on the CTX and the type of interactions. Altogether, our results suggested six clusters of consensus aptamer sequences from the phylogenetic tree analysis. Among the six aptamer models generated from their respective consensus sequences, three aptamers demonstrated significant binding to CTX. Additionally, the RING analysis revealed that there were four common interacting regions between the six CTX-aptamer complexes. These four interacting regions were consistent with the CTX’s epitopes in our unpublished work. Moreover, the high binding affinity between the aptamer-CTX complexes also suggested that they were potential aptamers to antagonize CTX’s action. The current work provides insights into in silico approach to design aptamers that antagonize CTX-induced dermonecrosis. Three tRNA-based aptamers have been identified as potential aptamers, which showed strong interaction with CTX’s epitopes.