The SARS-CoV heptad repeat 2 exhibits pH-induced helix formation

The heptad repeats 1 and 2 of SARS-CoV spike, termed HR1 and HR2, play critical roles in viral entry. Moreover, HR1 and HR2 derived free peptides are inhibitors of SARS-CoV entry. In this work we used circular dichroism to show that HR2 helix formation is induced at pH 5, the pH of the endosome. In addition, we demonstrate that the HR2 helix is further stabilized at physiological ionic strengths. Together, these observations provide new insight into the mechanism of SARS-CoV entry and suggest that HR2 may be an attractive target for therapeutic intervention.

► The SARS-CoV S2-HR2 helix is stabilized at pH 5, the pH of the endosome.
► The SARS-CoV S2-HR2 helix is stabilized at physiological ionic strength.
► A novel model for SARS-CoV entry is presented.
► The observations for SARS-CoV HR2 may be applicable to other viruses including Influenza and Ebola.