A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Xia, Shuai; Yan, Lei; Xu, Wei; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Tseng, Chien-Te K.; Wang, Qian; Du, Lanying; Tan, Wenjie; Wilson, Ian A.; Jiang, Shibo; Yang, Bei; Lu, Lu

Currently, circulating HCoVs pose a potential threat to humans; moreover, it is almost certain that other zoonotic CoVs will be transmitted to humans in the future. The availability of HCoV-specific drugs with broad-spectrum inhibitory activity is therefore important for the prevention and control of a future HCoV epidemic. The EK1 fusion inhibitor peptide targeting the conserved site in the spike HR1, but not the hypervariable RBD region, has potent and broad inhibitory activity against multiple HCoV infections. EK1 through nasal administration exhibited effective and broadly anti-HCoV activity with a satisfactory safety profile in vivo. Hence, EK1 is a promising candidate for further development as an antiviral agent against infection of multiple HCoVs, especially for use in infants and the elderly, as well as immunocompromised patients, who would be more vulnerable to HCoV infections (53) (54) (55) (56) . Meanwhile, this study provides clues and methods for the development of peptide fusion inhibitors with potency and breadth in inhibiting infections by other highly pathogenic enveloped viruses with class I membrane fusion proteins, such as Ebola and Marburg viruses, Hendra and Nipah viruses, and influenza viruses. were preserved in our laboratory. The DNA sequence of the S protein of OC43 with a deletion of 17 amino acids in the C terminus was synthesized. DNA encoding 229E-S or NL63-S-18 (containing a C-terminal 18-amino acid deletion) was provided by F. Li. All peptides were synthesized by KareBay Biochem with a purity of >95% (tested by high-performance liquid chromatography). The EK1-scrambled sequence was "LKVLLYEEFKLLESLIMEILEYQKDSDIKENAEDTK."