{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:12:01Z","timestamp":1774559521669,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Combined hormone drugs are the basis for orally administered contraception. However, they are associated with severe side effects that are even more impactful for women in developing countries, where resources are limited. The risk of side effects may be reduced by non-hormonal small molecules which specifically target proteins involved in fertilization. In this study, we present a virtual docking experiment directed to discover molecules that target the crucial fertilization interactions of JUNO (oocyte) and IZUMO1 (sperm). We docked 913,000 molecules to two crystal structures of JUNO and ranked them on the basis of energy-related criteria. Of the 32 tested candidates, two molecules (i.e., Z786028994 and Z1290281203) demonstrated fertilization inhibitory effect in both an <jats:italic>in vitro<\/jats:italic> fertilization (IVF) assay in mice and an <jats:italic>in vitro<\/jats:italic> penetration of human sperm into hamster oocytes. Despite this clear effect on fertilization, these two molecules did not show JUNO\u2013IZUMO1 interaction blocking activity as assessed by AVidity-based EXtracellular Interaction Screening (AVEXIS). Therefore, further research is required to determine the mechanism of action of these two fertilization inhibitors.<\/jats:p>","DOI":"10.3389\/fcell.2022.824629","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T10:43:47Z","timestamp":1649673827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["In silico Docking Analysis for Blocking JUNO\u2010IZUMO1 Interaction Identifies Two Small Molecules that Block in vitro Fertilization"],"prefix":"10.3389","volume":"10","author":[{"given":"Nataliia","family":"Stepanenko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omri","family":"Wolk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrica","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin James","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natali","family":"Schachter-Safrai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiril","family":"Makedonski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Ouro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assaf","family":"Ben-Meir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosef","family":"Buganim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amiram","family":"Goldblum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nature18595","article-title":"Molecular Architecture of the Human Sperm IZUMO1 and Egg JUNO Fertilization Complex","volume":"534","author":"Aydin","year":"2016","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e82849","DOI":"10.1371\/journal.pone.0082849","article-title":"Applying Physics-Based Scoring to Calculate Free Energies of Binding for Single Amino Acid Mutations in Protein-Protein Complexes","volume":"8","author":"Beard","year":"2013","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"20140101","DOI":"10.1098\/rstb.2014.0101","article-title":"Cross-species Fertilization: the Hamster Egg Receptor, Juno, Binds the Human Sperm Ligand, Izumo1","volume":"370","author":"Bianchi","year":"2015","journal-title":"Phil. 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