Journal Article Research Support, Non-U.S. Gov't Epublish
PubMed: 40143271 DOI: 10.3390/v17030343
Structures of HCoV-OC43 HR1 Domain in Complex with Cognate HR2 or Analogue EK1 Peptide.
Viruses 17(3)
Authors: Xiuxiu He, Huanzhen Liu, Guang Yang, Lei Yan
Affiliations
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
- International Research Center of Synthetic Biology, Nanjing Normal University, Nanjing 210023, China.
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China. Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China. International Research Center of Synthetic Biology, Nanjing Normal University, Nanjing 210023, China.
Abstract
Human coronavirus OC43 (HCoV-OC43) is usually associated with common colds, but also related to severe disease in the frail. Its envelope glycoproteins spike (S) is responsible for host-cell attachment and membrane fusion. To understand the molecular basis of membrane fusion of HCoV-OC43, we solved the 3.34 Å crystal structure of the post-fusion state formed by two heptad repeat domains (HR1P and HR2P) of OC43-S. This fusion core comprises a parallel trimeric coiled coil of three HR1 helices with 61 Å at length, around which three HR2 helices are entwined in an antiparallel manner, as anticipated. Moreover, a pan-CoV fusion inhibitor EK1 derived from OC43-HR2P was also crystalized with OC43-HR1P in the resolution of 2.71 Å. Parallel comparisons rationalize the design of EK1, maintaining various hydrophobic and charged or hydrophilic interactions formed in the initial fusion core to stabilize the overall conformation. Together, our results not only reveal the critical intrahelical and interhelical interactions underlying the mechanism of action of OC43-S fusion, but also help our understanding on the mechanism of HCoV-OC43 inhibition by analogue HR2 mimic peptide.
MeSH
Coronavirus Oc43, Human, Virology, Membranes, Membrane Fusion, Virus Internalization