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We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum of activity against\n                    <jats:italic>Ng<\/jats:italic>\n                    including MDR isolates. By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). Resistance mutations in\n                    <jats:italic>Ng<\/jats:italic>\n                    map to the N-terminal cone domain of the \u03b1 subunit, which we show here is involved in forming an inhibited \u03b1\n                    <jats:sub>4<\/jats:sub>\n                    \u03b2\n                    <jats:sub>4<\/jats:sub>\n                    state in the presence of the \u03b2 subunit and allosteric effector dATP. Enzyme assays confirm that PTC-847 and PTC-672 inhibit\n                    <jats:italic>Ng<\/jats:italic>\n                    RNR and reveal that allosteric effector dATP potentiates the inhibitory effect. Oral administration of PTC-672 reduces\n                    <jats:italic>Ng<\/jats:italic>\n                    infection in a mouse model and may have therapeutic potential for treatment of\n                    <jats:italic>Ng<\/jats:italic>\n                    that is resistant to current drugs.\n                  <\/jats:p>","DOI":"10.7554\/elife.67447","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T06:01:05Z","timestamp":1644386465000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67447","source":"Crossref","is-referenced-by-count":15,"title":["Ribonucleotide reductase, a novel drug target for gonorrhea"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-8592","authenticated-orcid":true,"given":"Jana","family":"Narasimhan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jz67a83","id-type":"ROR","asserted-by":"publisher"}],"name":"PTC Therapeutics, Inc","place":["South 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