{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:33:31Z","timestamp":1790393611295,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            To complete the eradication of poliovirus and to protect unvaccinated people subsequently, the development of one or more antiviral drugs will be necessary. A set of five single-domain antibody fragments (variable parts of the heavy chain of a heavy-chain antibody [VHHs]) with an\n            <jats:italic>in vitro<\/jats:italic>\n            neutralizing activity against poliovirus type 1 was developed previously (B. Thys, L. Schotte, S. Muyldermans, U. Wernery, G. Hassanzadeh-Ghassabeh, and B. Rombaut, Antiviral Res 87:257\u2013264, 2010,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1016\/j.antiviral.2010.05.012\">http:\/\/dx.doi.org\/10.1016\/j.antiviral.2010.05.012<\/jats:ext-link>\n            ), and their mechanisms of action have been studied (L. Schotte, M. Strauss, B. Thys, H. Halewyck, D. J. Filman, M. Bostina, J. M. Hogle, and B. Rombaut, J Virol 88:4403\u20134413, 2014,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1128\/JVI.03402-13\">http:\/\/dx.doi.org\/10.1128\/JVI.03402-13<\/jats:ext-link>\n            ). In this study, neutralization escape mutants were selected for each VHH. Sequencing of the P1 region of the genome showed that amino acid substitutions are found in the four viral proteins of the capsid and that they are located both in proximity to the binding sites of the VHHs and in regions further away from the canyon and hidden beneath the surface. Characterization of the mutants demonstrated that they have single-cycle replication kinetics that are similar to those of their parental strain and that they are all drug (VHH) independent. Their resistant phenotypes are stable, as they do not regain full susceptibility to the VHH after passage over HeLa cells in the absence of VHH. They are all at least as stable as the parental strain against heat inactivation at 44\u00b0C, and three of them are even significantly (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) more resistant to heat inactivation. The resistant variants all still can be neutralized by at least two other VHHs and retain full susceptibility to pirodavir and 35-1F4.\n          <\/jats:p>","DOI":"10.1128\/aac.00878-15","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:24:53Z","timestamp":1432740293000},"page":"4695-4706","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of Poliovirus Neutralization Escape Mutants of Single-Domain Antibody Fragments (VHHs)"],"prefix":"10.1128","volume":"59","author":[{"given":"Lise","family":"Schotte","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Thys","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Filman","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Rombaut","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Hogle","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.45.5_Pt_1.575"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1955.tb42565.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1981.tb00095.x"},{"key":"e_1_3_2_5_2","volume-title":"Exploring the role of antiviral drugs in the eradication of polio: workshop report","author":"Committee on Development of a Polio Antiviral and its Potential Role in Global Poliomyelitis Eradication NRC","year":"2006","unstructured":"Committee on Development of a Polio Antiviral and its Potential Role in Global Poliomyelitis Eradication NRC. 2006. 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