Development of broad-spectrum pan-CoV fusion inhibitors would be an ideal way to cope with epidemics or pandemics caused by emerging HCoVs. The conservative amino acid sequence of the HR1 region across different CoVs has the potential to be a target domain for development of an inhibitor. Continuing to work on the HR1 and HR2 domains, Jiang’s group discovered that the peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, broadly inhibited fusion by multiple HCoVs. By optimization of this peptide, a pan-CoV fusion inhibitor, EK1, was generated. It could form a stable six-helix bundle (6-HB) structure with HR1s and showed significantly improved fusion-inhibitory activity and pharmaceutical properties [61]. The alignment of S protein in Fig. 1 exhibited 100% identity at the HR2 domains between the 2019-nCoV and SARS-CoV; however, they found 7 amino acid changes in the fusion core of the HR1, located in the EK1 binding motif. Fortunately, the substitutions were conservative replacements which would not dramatically disrupt the interactions between EK1 and HR1, meaning that EK1 would still have the potential to be an effective inhibitor for 2019-nCoV infection.