@article{open2981,
           month = {June},
           title = {A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein},
          author = {Bhavesh  Khatri and Ishika  Pramanick and Sameer Kumar  Malladi  and Raju S  Rajmani and Sahil  Kumar and Pritha  Ghosh  and Nayanika  Sengupta and R  Rahisuddin and Narender  Kumar  and S  Kumaran  and Rajesh P  Ringe and Raghavan  Varadarajan and Somnath  Dutta and Jayanta  Chatterjee},
       publisher = {NATURE },
            year = {2022},
            note = {The copyright of this article belongs to Nature},
         journal = {Nature Chemical Biology },
             url = {http://crdd.osdd.net/open/2981/},
        abstract = {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.}
}