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Broader use of Ab-based drugs is constrained because of their high production costs and frequent side effects. One promising approach to overcome these limitations is the use of highly diluted Abs, which are produced by gradual reduction of an Ab concentration to an extremely low level. This technology was used to create a group of drugs for the treatment of various diseases, depending on the specificity of the used Abs. Highly diluted Abs to IFN-\u03b3 (hd-anti\u2013IFN-\u03b3) have been demonstrated to be efficacious against influenza and other respiratory infections in a variety of preclinical and clinical studies. In the current study, we provide evidence for a possible mechanism of action of hd-anti\u2013IFN-\u03b3. Using high-resolution solution nuclear magnetic resonance spectroscopy, we show that the drug induced conformational changes in the IFN-\u03b3 molecule. Chemical shift changes occurred in the amino acids located primarily at the dimer interface and at the C-terminal region of IFN-\u03b3. These molecular changes could be crucial for the function of the protein, as evidenced by an observed hd-anti\u2013IFN-\u03b3\u2013induced increase in the specific binding of IFN-\u03b3 to its receptor in U937 cells, enhanced induced production of IFN-\u03b3 in human PBMC culture, and increased survival of influenza A\u2013infected mice.<\/jats:p>","DOI":"10.4049\/jimmunol.2000098","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T20:35:22Z","timestamp":1596054922000},"page":"1345-1354","source":"Crossref","is-referenced-by-count":60,"title":["Insights into the Mechanism of Action of Highly Diluted Biologics"],"prefix":"10.1093","volume":"205","author":[{"given":"Sergey A","family":"Tarasov","sequence":"first","affiliation":[{"name":"OOO \u201cNPF \u201cMateria Medica Holding,\u201d \u00a0 127473 Moscow ,","place":["Russian Federation"]},{"name":"The Institute of General Pathology and Pathophysiology , 125315 Moscow ,","place":["Russian Federation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7547-1008","authenticated-orcid":false,"given":"Evgeniy A","family":"Gorbunov","sequence":"additional","affiliation":[{"name":"OOO \u201cNPF \u201cMateria Medica Holding,\u201d \u00a0 127473 Moscow ,","place":["Russian Federation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena S","family":"Don","sequence":"additional","affiliation":[{"name":"OOO \u201cNPF \u201cMateria Medica Holding,\u201d \u00a0 127473 Moscow ,","place":["Russian Federation"]},{"name":"The Institute of General Pathology and Pathophysiology , 125315 Moscow ,","place":["Russian Federation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra G","family":"Emelyanova","sequence":"additional","affiliation":[{"name":"OOO \u201cNPF \u201cMateria Medica Holding,\u201d \u00a0 127473 Moscow ,","place":["Russian Federation"]},{"name":"The Institute of General Pathology and Pathophysiology , 125315 Moscow ,","place":["Russian Federation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander L","family":"Kovalchuk","sequence":"additional","affiliation":[{"name":"OOO \u201cNPF \u201cMateria Medica Holding,\u201d \u00a0 127473 Moscow ,","place":["Russian Federation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveena","family":"Yanamala","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Sylvia S","family":"Schleker","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Klein-Seetharaman","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reno","family":"Groenestein","sequence":"additional","affiliation":[{"name":"U-CyTech biosciences , 3584 CM Utrecht ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Tafani","sequence":"additional","affiliation":[{"name":"Apcis , 94700 Maisons Alfort ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meide","sequence":"additional","affiliation":[{"name":"U-CyTech biosciences , 3584 CM Utrecht ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg I","family":"Epstein","sequence":"additional","affiliation":[{"name":"OOO \u201cNPF \u201cMateria Medica Holding,\u201d \u00a0 127473 Moscow ,","place":["Russian Federation"]},{"name":"The Institute of General Pathology and Pathophysiology , 125315 Moscow ,","place":["Russian Federation"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"2025030417504829000_r1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.tibtech.2018.05.014","article-title":"The increasingly human and profitable monoclonal antibody market","volume":"37","author":"Grilo","year":"2019","journal-title":"Trends Biotechnol."},{"key":"2025030417504829000_r2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.4314\/tjpr.v16i3.29","article-title":"Monoclonal antibodies: a review of therapeutic applications and future prospects","volume":"16","author":"Mahmuda","year":"2017","journal-title":"Trop. 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