Refining the Na V 1 .7 pharmacophore of a class of venom‐derived peptide inhibitors via a combination of in silico screening and rational engineering
Year: 2025
Type: article
Abstract: Ion channels are among the main targets of venom peptides. Extensive functional screening has identified a number of these peptides as modulators of the voltage‐gated sodium channel subtype Na V 1.7, a potential target for the treatment of chronic pain. In this study, we used a bioinformatic approach that can automatically identify Na V 1.7 gating modifier toxins from sequence information alone. The method further enables the incorporation of evolutionarily accessible sequence space in structure–activity relationship studies. The in silico method identified a putative Na V 1.7 inhibitor, μ‐theraphotoxin Cg4a, which we produced recombinantly and confirmed as a Na V 1.7 inhibitor. Using structural and mutagenesis studies, we propose an improved definition of the pharmacophore of this class of Na V 1.7 inhibitors, aiding future in silico screening and classification of Na V 1.7 inhibitors.
Source: FEBS Letters
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,980
Awards: Mechanistic and pharmacological insights into peripheral sensory neuron function in physiological and pathological pain, Novel analgesics for treating chronic pain, G168634317, Unravelling the structural evolution of centipede toxins, Understanding how toxins interact with lipid membranes and ion channels, A pharmacological approach to define the contribution of Nav1.7 to pain pathways, G5769756091
OpenAlex ID: W4408997634