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Biol."],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>An integrated computational approach to in silico drug design was used to identify novel HIV-1 fusion inhibitor scaffolds mimicking broadly neutralizing antibody (bNab) 10E8 targeting the membrane proximal external region (MPER) of the HIV-1 gp41 protein. This computer-based approach included (i) generation of pharmacophore models representing 3D-arrangements of chemical functionalities that make bNAb 10E8 active towards the gp41 MPER segment, (ii) shape and pharmacophore-based identification of the 10E8-mimetic candidates by a web-oriented virtual screening platform pepMMsMIMIC, (iii) high-throughput docking of the identified compounds with the gp41 MPER peptide, and (iv) molecular dynamics simulations of the docked structures followed by binding free energy calculations. As a result, eight hits-able to mimic pharmacophore properties of bNAb 10E8 by specific and effective interactions with the MPER region of the HIV-1 protein gp41 were selected as the most probable 10E8-mimetic candidates. Similar to 10E8, the predicted compounds target the critically important residues of a highly conserved hinge region of the MPER peptide that provides a conformational flexibility necessary for its functioning in cell-virus membrane fusion process. In light of the data obtained, the identified small molecules may present promising HIV-1 fusion inhibitor scaffolds for the design of novel potent antiviral drugs.<\/jats:p>","DOI":"10.1142\/s0219720018400073","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T09:43:40Z","timestamp":1516009420000},"page":"1840007","source":"Crossref","is-referenced-by-count":5,"title":["Potential HIV-1 fusion inhibitors mimicking gp41-specific broadly neutralizing antibody 10E8: In silico discovery and prediction of antiviral potency"],"prefix":"10.1142","volume":"16","author":[{"given":"Alexander M.","family":"Andrianov","sequence":"first","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Kuprevich Street 5\/2 220141 Minsk, Republic of Belarus"}]},{"given":"Ivan A.","family":"Kashyn","sequence":"additional","affiliation":[{"name":"United Institute of Informatics Problems, National Academy of Sciences of Belarus, 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