{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T02:04:23Z","timestamp":1780538663581,"version":"3.54.1"},"reference-count":74,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["23-15-00471"],"award-info":[{"award-number":["23-15-00471"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite global vaccination efforts, poliomyelitis continues to cause paralytic cases, highlighting the need for alternative therapeutic approaches. Nanobodies offer significant advantages over conventional antibodies due to their small size, stability, and low immunogenicity, yet few have been developed specifically against poliovirus. This study presents a fully computational pipeline for de novo design of nanobodies targeting Virus Protein 3 (VP3) of the Poliovirus I Sabin strain. Our integrated approach employed Ig-VAE for scaffold generation, ProteinMPNN and RFantibody for sequence design, tFold-Ab\/Ag for structure prediction, multi-platform molecular docking (Rfantibody, Rosetta3, ClusPro2, ReplicaDock 2.0), molecular dynamics simulations, and humanization tools. The pipeline identified three humanized nanobodies (scFv-0389-304-6H, scFv-0389-459-5H, and scFv-0743-166-7\/H) that demonstrated strong binding to VP3 with binding free energies of \u221237.66 \u00b1 10.35, \u221240.11 \u00b1 20.01, and \u221248.62 \u00b1 11.21 kcal\/mol, respectively. All designs exhibited favorable physicochemical properties and high solubility. Notably, nanobodies humanized prior to CDR-loop design (scFv-0743-166-7\/H) showed superior stability, binding affinity, and structural similarity to experimentally validated nanobodies. This work demonstrates the feasibility of a fully computational approach for designing promising nanobodies against viral targets, providing an alternative to traditional methods with potential applications in drug design.<\/jats:p>","DOI":"10.3390\/ijms26199262","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:09:42Z","timestamp":1758614982000},"page":"9262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NanoDeNovo: De Novo Design of Anti-Poliovirus I Sabin Strain Nanobodies by Semi-Automated Computational Pipeline"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5159-5796","authenticated-orcid":false,"given":"Danil D.","family":"Kotelnikov","sequence":"first","affiliation":[{"name":"Institute of Biomedical Chemistry, 10\/8 Pogodinskaya Str., 119121 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8642-7251","authenticated-orcid":false,"given":"Katerina S.","family":"Tatarinova","sequence":"additional","affiliation":[{"name":"Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 31-4, Leninsky Prospect, 119071 Moscow, Russia"},{"name":"Higher Chemical College, Dmitry Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, 125047 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4753-7588","authenticated-orcid":false,"given":"Dmitry D.","family":"Zhdanov","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, 10\/8 Pogodinskaya Str., 119121 Moscow, Russia"},{"name":"Department of Biochemistry, People\u2019s Friendship University of Russia Named After Patrice Lumumba (RUDN University), 6 Miklukho-Maklaya Str., 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lopez Cavestany, R., Eisenhawer, M., Diop, O.M., Verma, H., Quddus, A., and Mach, O. 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