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ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 activation. Here we used available structural and experimental data to guide Rosetta design of potent and selective ProTx-II-based peptide inhibitors of human Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 channels. Functional testing of designed peptides using electrophysiology identified the PTx2-3127 and PTx2-3258 peptides with IC\n                    <jats:sub>50<\/jats:sub>\n                    s of 7 nM and 4 nM for hNa\n                    <jats:sub>V<\/jats:sub>\n                    1.7 and more than 1000-fold selectivity over human Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1, Na\n                    <jats:sub>V<\/jats:sub>\n                    1.3, Na\n                    <jats:sub>V<\/jats:sub>\n                    1.4, Na\n                    <jats:sub>V<\/jats:sub>\n                    1.5, Na\n                    <jats:sub>V<\/jats:sub>\n                    1.8, and Na\n                    <jats:sub>V<\/jats:sub>\n                    1.9 channels. PTx2-3127 inhibits Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 currents in mouse and human sensory neurons and shows efficacy in rat models of chronic and thermal pain when administered intrathecally. Rationally designed peptide inhibitors of human Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 channels have transformative potential to define a new class of biologics to treat pain.\n                  <\/jats:p>","DOI":"10.7554\/elife.81727","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T08:02:46Z","timestamp":1672214566000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.81727","source":"Crossref","is-referenced-by-count":33,"title":["Computational design of peptides to target NaV1.7 channel with high potency and selectivity for the treatment of pain"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-7807","authenticated-orcid":true,"given":"Phuong T","family":"Nguyen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05rrcem69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology and Membrane Biology, University of California 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