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Theta defensins, cyclic peptides, inhibit the formation of these bundles by binding to the GP41 CHR region. RC101, a synthetic analog of theta-defensin molecules, exhibits activity against various HIV subtypes. Molecular docking of the CHR and RC101 was done using MDockPeP and Hawdock server. The type of bonds and the essential amino acids in binding were identified using AlphaFold3, CHIMERA, RING, and CYTOSCAPE. Mutable amino acids within the peptide were determined using the CUPSAT and Duet. Thirty-two new peptides were designed, and their interaction with the CHR of the gp41 was analyzed. The physicochemical properties, toxicity, allergenicity, and antigenicity of peptides were also investigated. Most of the designed peptides exhibited higher binding affinities to the target compared to RC101; notably, peptides 1 and 4 had the highest binding affinity and demonstrated a greater percentage of interactions with critical amino acids of CHR. Peptides A and E displayed the best physiochemical properties among designed peptides. The designed peptides may present a new generation of anti-HIV drugs, which may reduce the likelihood of drug resistance.<\/jats:p>","DOI":"10.1515\/jib-2023-0053","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T03:19:22Z","timestamp":1742267962000},"source":"Crossref","is-referenced-by-count":2,"title":["Designing an optimized theta-defensin peptide for HIV therapy using in-silico approaches"],"prefix":"10.1515","volume":"22","author":[{"given":"Zahra","family":"Mosalanejad","sequence":"first","affiliation":[{"name":"Biotechnology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran"}]},{"given":"Seyed Nooreddin","family":"Faraji","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine , 48435 Shiraz University of Medical Sciences , Shiraz , Iran"},{"name":"Nush Darouye Hooshmand Pars Company, Biotechnology Incubator , 48435 Shiraz University of Medical Sciences , Shiraz , Iran"}]},{"given":"Mohammad Reza","family":"Rahbar","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center , 48435 Shiraz University of Medical Sciences , Shiraz , Iran"}]},{"given":"Ahmad","family":"Gholami","sequence":"additional","affiliation":[{"name":"NoushDaru Intelligent Pars Company , Biotechnology Incubator , Shiraz University of Medical Sciences , Shiraz , Iran ."},{"name":"Pharmaceutical Sciences Research Center , 48435 Shiraz University of Medical Sciences , Shiraz , Iran"},{"name":"Department of Pharmaceutical Biotechnology, School of Pharmacy , 48435 Shiraz University of Medical Sciences , Shiraz , Iran"}]}],"member":"374","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"2025080610581969172_j_jib-2023-0053_ref_001","doi-asserted-by":"crossref","unstructured":"van Schalkwyk, C, Mahy, M, Johnson, LF, Imai-Eaton, JW. Updated data and methods for the 2023 UNAIDS HIV estimates. J Acquir Immune Defic Syndr 2024;95. https:\/\/doi.org\/10.1097\/qai.0000000000003344.","DOI":"10.1097\/QAI.0000000000003344"},{"key":"2025080610581969172_j_jib-2023-0053_ref_002","doi-asserted-by":"crossref","unstructured":"Gilbert, PB, McKeague, IW, Eisen, G, Mullins, C, Gu\u00e9ye-Ndiaye, A, Mboup, S, et al.. Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal. Stat Med 2003;22:573\u201393. https:\/\/doi.org\/10.1002\/sim.1342.","DOI":"10.1002\/sim.1342"},{"key":"2025080610581969172_j_jib-2023-0053_ref_003","doi-asserted-by":"crossref","unstructured":"Yamaguchi, J, Vallari, A, McArthur, C, Sthreshley, L, Cloherty, GA, Berg, MG, et al.. Brief report: complete genome sequence of CG-0018a-01 establishes HIV-1 subtype L. 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J Biochem 1980;88:1895\u20138."},{"key":"2025080610581969172_j_jib-2023-0053_ref_054","doi-asserted-by":"crossref","unstructured":"Korber, B, Gaschen, B, Yusim, K, Thakallapally, R, Kesmir, C, Detours, V. Evolutionary and immunological implications of contemporary HIV-1 variation. Br Med Bull 2001;58:19\u201342. https:\/\/doi.org\/10.1093\/bmb\/58.1.19.","DOI":"10.1093\/bmb\/58.1.19"},{"key":"2025080610581969172_j_jib-2023-0053_ref_055","doi-asserted-by":"crossref","unstructured":"Elangovan, R, Jenks, M, Yun, J, Dickson-Tetteh, L, Kirtley, S, Hemelaar, J, et al.. Global and regional estimates for subtype-specific therapeutic and prophylactic HIV-1 vaccines: a modeling study. Front Microbiol 2021;12:690647. https:\/\/doi.org\/10.3389\/fmicb.2021.690647.","DOI":"10.3389\/fmicb.2021.690647"},{"key":"2025080610581969172_j_jib-2023-0053_ref_056","doi-asserted-by":"crossref","unstructured":"Chan, DC, Fass, D, Berger, JM, Kim, PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell 1997;89:263\u201373. https:\/\/doi.org\/10.1016\/s0092-8674(00)80205-6.","DOI":"10.1016\/S0092-8674(00)80205-6"},{"key":"2025080610581969172_j_jib-2023-0053_ref_057","doi-asserted-by":"crossref","unstructured":"Hemelaar, J, Elangovan, R, Yun, J, Dickson-Tetteh, L, Fleminger, I, Kirtley, S, et al.. Global and regional molecular epidemiology of HIV-1, 1990\u20132015: a systematic review, global survey, and trend analysis. Lancet Infect Dis 2019;19:143\u201355. https:\/\/doi.org\/10.1016\/s1473-3099(18)30647-9.","DOI":"10.1016\/S1473-3099(18)30647-9"},{"key":"2025080610581969172_j_jib-2023-0053_ref_058","doi-asserted-by":"crossref","unstructured":"Allen, WJ, Rizzo, RC. Computer-aided approaches for targeting HIVgp41. Biology 2012;1:311\u201338. https:\/\/doi.org\/10.3390\/biology1020311.","DOI":"10.3390\/biology1020311"},{"key":"2025080610581969172_j_jib-2023-0053_ref_059","doi-asserted-by":"crossref","unstructured":"Pancera, M, Zhou, T, Druz, A, Georgiev, IS, Soto, C, Gorman, J, et al.. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 2014;514:455\u201361. https:\/\/doi.org\/10.1038\/nature13808.","DOI":"10.1038\/nature13808"},{"key":"2025080610581969172_j_jib-2023-0053_ref_060","doi-asserted-by":"crossref","unstructured":"Rashidi, S, Faraji, SN, Mamaghani, AJ, Hatam, S, Kazemi, B, Bemani, P, et al.. Bioinformatics analysis for the purpose of designing a novel multi-epitope DNA vaccine against Leishmania major. Sci Rep 2022;12:18119. https:\/\/doi.org\/10.1038\/s41598-022-22646-7.","DOI":"10.1038\/s41598-022-22646-7"},{"key":"2025080610581969172_j_jib-2023-0053_ref_061","doi-asserted-by":"crossref","unstructured":"Hajighahramani, N, Eslami, M, Negahdaripour, M, Ghoshoon, MB, Dehshahri, A, Erfani, N, et al.. Computational design of a chimeric epitope-based vaccine to protect against Staphylococcus aureus infections. Mol Cell Probes 2019;46:101414. https:\/\/doi.org\/10.1016\/j.mcp.2019.06.004.","DOI":"10.1016\/j.mcp.2019.06.004"},{"key":"2025080610581969172_j_jib-2023-0053_ref_062","doi-asserted-by":"crossref","unstructured":"Cheng, DQ, Li, Y, Huang, JF. Molecular evolution of the primate \u03b1-\/\u03b8-defensin multigene family. PLoS One 2014;9:e97425. https:\/\/doi.org\/10.1371\/journal.pone.0097425.","DOI":"10.1371\/journal.pone.0097425"},{"key":"2025080610581969172_j_jib-2023-0053_ref_063","doi-asserted-by":"crossref","unstructured":"Wang, Q, Wang, W, Zheng, J, Tabibian, S, Xie, Y, Song, J, et al.. Paradoxical effects of two theta-defensins on HIV type 1 infection. AIDS Res Hum Retrovir 2007;23:508\u201314. https:\/\/doi.org\/10.1089\/aid.2006.0119.","DOI":"10.1089\/aid.2006.0119"},{"key":"2025080610581969172_j_jib-2023-0053_ref_064","doi-asserted-by":"crossref","unstructured":"Penberthy, WT, Chari, S, Cole, AL, Cole, AM. Retrocyclins and their activity against HIV-1. Cell Mol Life Sci 2011;68:2231\u201342. https:\/\/doi.org\/10.1007\/s00018-011-0715-5.","DOI":"10.1007\/s00018-011-0715-5"},{"key":"2025080610581969172_j_jib-2023-0053_ref_065","doi-asserted-by":"crossref","unstructured":"Hajizade, MS, Raee, MJ, Faraji, SN, Farvadi, F, Kabiri, M, Eskandari, S, et al.. Targeted drug delivery to the thrombus by fusing streptokinase with a fibrin-binding peptide (CREKA): an in silico study. Ther Deliv 2024;15:399\u2013411. https:\/\/doi.org\/10.4155\/tde-2023-0107.","DOI":"10.4155\/tde-2023-0107"},{"key":"2025080610581969172_j_jib-2023-0053_ref_066","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Castro, R, G\u00f3mez-Lim, MA, Plisson, F. Cysteine-rich peptides: hyperstable scaffolds for protein engineering. Chembiochem 2021;22:961\u201373. https:\/\/doi.org\/10.1002\/cbic.202000634.","DOI":"10.1002\/cbic.202000634"},{"key":"2025080610581969172_j_jib-2023-0053_ref_067","unstructured":"Gholami, A, Rasoul-Amini, S, Ebrahiminezhad, A, Abootalebi, N, Niroumand, U, Ebrahimi, N, et al.. Magnetic properties and antimicrobial effect of amino and lipoamino acid coated iron oxide nanoparticles. Minerva Biotecnol 2016;28:177\u201386."},{"key":"2025080610581969172_j_jib-2023-0053_ref_068","doi-asserted-by":"crossref","unstructured":"Leikina, E, Delanoe-Ayari, H, Melikov, K, Cho, MS, Chen, A, Waring, AJ, et al.. Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins. Nat Immunol 2005;6:995\u20131001. https:\/\/doi.org\/10.1038\/ni1248.","DOI":"10.1038\/ni1248"},{"key":"2025080610581969172_j_jib-2023-0053_ref_069","doi-asserted-by":"crossref","unstructured":"Penberthy, WT, Chari, S, Cole, AL, Cole, AM. Retrocyclins and their activity against HIV-1. Cell Mol Life Sci 2011;68:2231\u201342. https:\/\/doi.org\/10.1007\/s00018-011-0715-5.","DOI":"10.1007\/s00018-011-0715-5"},{"key":"2025080610581969172_j_jib-2023-0053_ref_070","doi-asserted-by":"crossref","unstructured":"Li, W, Lu, L, Li, W, Jiang, S. Small-molecule HIV-1 entry inhibitors targeting gp120 and gp41: a patent review (2010\u20132015). Expert Opin Ther Pat 2017;27:707\u201319. https:\/\/doi.org\/10.1080\/13543776.2017.1281249.","DOI":"10.1080\/13543776.2017.1281249"},{"key":"2025080610581969172_j_jib-2023-0053_ref_071","doi-asserted-by":"crossref","unstructured":"Yi, HA, Fochtman, BC, Rizzo, RC, Jacobs, A. Inhibition of HIV entry by targeting the envelope transmembrane subunit gp41. Curr HIV Res 2016;14:283\u201394. https:\/\/doi.org\/10.2174\/1570162x14999160224103908.","DOI":"10.2174\/1570162X14999160224103908"},{"key":"2025080610581969172_j_jib-2023-0053_ref_072","doi-asserted-by":"crossref","unstructured":"Frey, G, Rits-Volloch, S, Zhang, XQ, Schooley, RT, Chen, B, Harrison, SC. Small molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion. Proc Natl Acad Sci USA 2006;103:13938\u201343. https:\/\/doi.org\/10.1073\/pnas.0601036103.","DOI":"10.1073\/pnas.0601036103"},{"key":"2025080610581969172_j_jib-2023-0053_ref_073","unstructured":"Santos, A, Da Silva, M, Napole\u00e3o, T, Paiva, P, Correia, MS, Coelho, L. Lectins: function, structure, biological properties and potential applications. Curr Top Pept Protein Res 2014;15:41\u201362."},{"key":"2025080610581969172_j_jib-2023-0053_ref_074","doi-asserted-by":"crossref","unstructured":"He, Y, Liu, S, Li, J, Lu, H, Qi, Z, Liu, Z, et al.. Conserved salt bridge between the N-and C-terminal heptad repeat regions of the human immunodeficiency virus type 1 gp41 core structure is critical for virus entry and inhibition. J Virol 2008;82:11129\u201339. https:\/\/doi.org\/10.1128\/jvi.01060-08.","DOI":"10.1128\/JVI.01060-08"},{"key":"2025080610581969172_j_jib-2023-0053_ref_075","doi-asserted-by":"crossref","unstructured":"Geng, X, Liu, Z, Yu, D, Qin, B, Zhu, Y, Cui, S, et al.. Conserved residue Asn-145 in the C-terminal heptad repeat region of HIV-1 gp41 is critical for viral fusion and regulates the antiviral activity of fusion inhibitors. Viruses 2019;11:609. https:\/\/doi.org\/10.3390\/v11070609.","DOI":"10.3390\/v11070609"},{"key":"2025080610581969172_j_jib-2023-0053_ref_076","doi-asserted-by":"crossref","unstructured":"Cary, DR, Ohuchi, M, Reid, PC, Masuya, K. Constrained peptides in drug discovery and development. J Synth Org Chem 2017;75:1171\u20138. https:\/\/doi.org\/10.5059\/yukigoseikyokaishi.75.1171.","DOI":"10.5059\/yukigoseikyokaishi.75.1171"},{"key":"2025080610581969172_j_jib-2023-0053_ref_077","doi-asserted-by":"crossref","unstructured":"Aisenbrey, C, Bechinger, B. Structure, interactions and membrane topology of HIV gp41 ectodomain sequences. Biochim Biophys Acta Biomembr 2020;1862:183274. https:\/\/doi.org\/10.1016\/j.bbamem.2020.183274.","DOI":"10.1016\/j.bbamem.2020.183274"},{"key":"2025080610581969172_j_jib-2023-0053_ref_078","unstructured":"Hopkins, E, Sanvictores, T, Sharma, S. Physiology, acid base balance. Treasure Island, FL: StatPearls Publishing; 2023."},{"key":"2025080610581969172_j_jib-2023-0053_ref_079","doi-asserted-by":"crossref","unstructured":"Al Musaimi, O, Lombardi, L, Williams, DR, Albericio, F. Strategies for improving peptide stability and delivery. Pharmaceuticals 2022;15:1283. https:\/\/doi.org\/10.3390\/ph15101283.","DOI":"10.3390\/ph15101283"},{"key":"2025080610581969172_j_jib-2023-0053_ref_080","doi-asserted-by":"crossref","unstructured":"Morrison, C. Constrained peptides\u2019 time to shine? Nat Rev Drug Discov 2018;17:531\u20134. https:\/\/doi.org\/10.1038\/nrd.2018.125.","DOI":"10.1038\/nrd.2018.125"},{"key":"2025080610581969172_j_jib-2023-0053_ref_081","doi-asserted-by":"crossref","unstructured":"Brandenberg, OF, Magnus, C, Rusert, P, Regoes, RR, Trkola, A. Different infectivity of HIV-1 strains is linked to number of envelope trimers required for entry. PLoS Pathog 2015;11:e1004595. https:\/\/doi.org\/10.1371\/journal.ppat.1004595.","DOI":"10.1371\/journal.ppat.1004595"},{"key":"2025080610581969172_j_jib-2023-0053_ref_082","doi-asserted-by":"crossref","unstructured":"Jurado, S, Cano-Mu\u00f1oz, M, Polo-Meg\u00edas, D, Conejero-Lara, F, Morel, B. Thermodynamic dissection of the interface between HIV-1 gp41 heptad repeats reveals cooperative interactions and allosteric effects. Arch Biochem Biophys 2020;688:108401. https:\/\/doi.org\/10.1016\/j.abb.2020.108401.","DOI":"10.1016\/j.abb.2020.108401"},{"key":"2025080610581969172_j_jib-2023-0053_ref_083","doi-asserted-by":"crossref","unstructured":"Conibear, AC, Bochen, A, Rosengren, KJ, Stupar, P, Wang, C, Kessler, H, et al.. The cyclic cystine ladder of theta-defensins as a stable, bifunctional scaffold: a proof-of-concept study using the integrin-binding RGD motif. Chembiochem 2014;15:451\u20139. https:\/\/doi.org\/10.1002\/cbic.201300568.","DOI":"10.1002\/cbic.201300568"},{"key":"2025080610581969172_j_jib-2023-0053_ref_084","doi-asserted-by":"crossref","unstructured":"Jiang, S, Lin, K, Strick, N, Neurath, AR. HIV-1 inhibition by a peptide. Nature 1993;365:113. https:\/\/doi.org\/10.1038\/365113a0.","DOI":"10.1038\/365113a0"},{"key":"2025080610581969172_j_jib-2023-0053_ref_085","doi-asserted-by":"crossref","unstructured":"Root, MJ, Kay, MS, Kim, PS. Protein design of an HIV-1 entry inhibitor. Science 2001;291:884\u20138. https:\/\/doi.org\/10.1126\/science.1057453.","DOI":"10.1126\/science.1057453"},{"key":"2025080610581969172_j_jib-2023-0053_ref_086","doi-asserted-by":"crossref","unstructured":"Jurado, S, Moog, C, Cano-Mu\u00f1oz, M, Schmidt, S, Laumond, G, Ruocco, V, et al.. Probing vulnerability of the gp41 C-terminal heptad repeat as target for miniprotein HIV inhibitors. J Mol Biol 2020;432:5577\u201392. https:\/\/doi.org\/10.1016\/j.jmb.2020.08.010.","DOI":"10.1016\/j.jmb.2020.08.010"},{"key":"2025080610581969172_j_jib-2023-0053_ref_087","doi-asserted-by":"crossref","unstructured":"Weng, G, Gao, J, Wang, Z, Wang, E, Hu, X, Yao, X, et al.. Comprehensive evaluation of fourteen docking programs on protein\u2013peptide complexes. 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