Novel Engineered SARS-CoV-2 HR1 Trimer Exhibits Improved Potency and Broad-Spectrum Activity against SARS-CoV-2 and Its Variants
Wenwen Bi, Guilin Chen, Bobo Dang
Abstract
Peptides derived from the SARS-CoV-2 HR1 region are generally poor inhibitors. Here, we constructed a trimeric peptide HR1MFd by fusing the trimerization motif foldon to the C terminus of the HR1 peptide. HR1MFd was highly effective in blocking transductions by SARS-CoV-2, SARS-CoV-2 variants, SARS-CoV, and MERS-CoV pseudoviruses. In comparison with HR1M, HR1MFd adopted a much higher helical conformation, better thermostability, increased affinity to the viral HR2 domain, and better inhibition of S protein-mediated cell-cell fusion. Overall, HR1MFd provides the information to develop effective HR1-derived peptides as fusion inhibitors against SARS-CoV-2 and its variants.
Topics & Concepts
BiologyTrimerSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)VirologyPeptideBroad spectrumCoronavirus disease 2019 (COVID-19)2019-20 coronavirus outbreakPotencyPeptide sequenceGeneticsIn vitroBiochemistryInfectious disease (medical specialty)GeneChemistryCombinatorial chemistryMedicineOutbreakDimerOrganic chemistryPathologyDiseaseSARS-CoV-2 and COVID-19 ResearchAdvanced biosensing and bioanalysis techniquesRNA Interference and Gene Delivery