A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike
Citations Over TimeTop 1% of 2019 papers
Abstract
Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.
Related Papers
- → Quantitative determination of mechanical stability in the novel coronavirus spike protein(2020)67 cited
- → [Spike protein in the detection and treatment of novel coronavirus].(2020)5 cited
- → Identification of immunogenic determinants of the spike protein of SARS-like coronavirus(2013)7 cited
- → Structural Analysis of Spike Protein Mutations in the SARS-CoV-2 P.3 Variant(2021)11 cited
- Study on Characteristics of SARS Coronavirus Based on Z Curve(2005)