Dear editor, Emerging and re-emerging pathogens are global challenges for public health [1]. Since the end of 2019, a cluster of coronavirus disease 2019 (COVID-19) cases have been reported, with a novel coronavirus (CoV), HCoV-19 as the causative agent [2]. Under exceptional control measures by the Chinese government, only a few new local cases have been confirmed recently. However, the virus has swiftly become a global pandemic and caused> 234,000 confirmed cases, including> 9800-related deaths globally as of 20 March 2020 (https://www. who. int/). Currently, there are no vaccines or therapeutics available. Based on the knowledge on CoVs, the infection of HCoV-19 is mediated by first receptor recognition and then membrane fusion [3]. The spike (S) protein, which is likely to be cleaved into S1 and S2, is responsible for the two processes. S1 directly interacts with the receptor. The fusion is mediated by a 6-helix bundle fusion core constituted by the characteristic element called heptad repeats (HRs), HR1 and HR2 in S2. Peptides derived from HRs of SARS-CoV and MERS-CoV have been proven to be capable of inhibiting virus fusion and thereafter preventing virus infection [4, 5]. In this study, we solved the crystal structure of fusion core of HCoV-19, and screened a panel of peptides that may potently inhibit virus infection. We first positioned the HR sequences of HCoV-19 to residues E918-L966 for the HR1 region and residues

D1163-L1203 for the HR2 region, using the SARS-CoV and MERS-CoV sequences as references [4, 6](Figure 1 (a)). Recombinant proteins of fusion core, which consists HR1 and HR2 linked with a peptide linker, were expressed in E. coli cells and set up for crystal screening (Figure S1).