<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein"^^ . "Protein tertiary structure mimetics are valuable tools to target large protein-protein interaction interfaces. Here, we demonstrate a strategy for designing dimeric helix-hairpin motifs from a previously reported three-helix-bundle miniprotein that targets the receptor-binding domain (RBD) of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Through truncation of the third helix and optimization of the interhelical loop residues of the miniprotein, we developed a thermostable dimeric helix-hairpin. The dimeric four-helix bundle competes with the human angiotensin-converting enzyme 2 (ACE2) in binding to RBD with 2:2 stoichiometry. Cryogenic-electron microscopy revealed the formation of dimeric spike ectodomain trimer by the four-helix bundle, where all the three RBDs from either spike protein are attached head-to-head in an open conformation, revealing a novel mechanism for virus neutralization. The proteomimetic protects hamsters from high dose viral challenge with replicative SARS-CoV-2 viruses, demonstrating the promise of this class of peptides that inhibit protein-protein interaction through target dimerization."^^ . "2022-06-02" . . "NATURE "^^ . . . "Nature Chemical Biology "^^ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "Pritha "^^ . "Ghosh "^^ . "Pritha Ghosh "^^ . . "Sameer Kumar "^^ . "Malladi "^^ . "Sameer Kumar Malladi "^^ . . "Ishika "^^ . "Pramanick"^^ . "Ishika Pramanick"^^ . . "Raghavan "^^ . "Varadarajan"^^ . "Raghavan Varadarajan"^^ . . "Raju S "^^ . "Rajmani"^^ . "Raju S Rajmani"^^ . . "S "^^ . "Kumaran "^^ . "S Kumaran "^^ . . "Bhavesh "^^ . "Khatri"^^ . "Bhavesh Khatri"^^ . . "Somnath "^^ . "Dutta"^^ . "Somnath Dutta"^^ . . "Nayanika "^^ . "Sengupta"^^ . "Nayanika Sengupta"^^ . . "Jayanta "^^ . "Chatterjee"^^ . "Jayanta Chatterjee"^^ . . "Rajesh P "^^ . "Ringe"^^ . "Rajesh P Ringe"^^ . . "Sahil "^^ . "Kumar"^^ . "Sahil Kumar"^^ . . "Narender "^^ . "Kumar "^^ . "Narender Kumar "^^ . . "R "^^ . "Rahisuddin"^^ . "R Rahisuddin"^^ . . . . . "HTML Summary of #2981 \n\nA dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein\n\n" . "text/html" . . . "QR Microbiology"@en . .