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

The pseudovirus assay is a good model to mimic the process of virus entry into the target cell and has been widely used in previous studies to assess the inhibitory activity of antiviral agents against related CoV infection (33) . We also used here pseudovirus assays to assess the inhibitory activity of EK1 against different pseudotyped HCoVs. In a MERS-CoV pseudovirus infection assay, both EK1 and MERS-HR2P showed inhibitory activity with IC 50 values of 0.26 and 1.06 M, respectively (Fig. 2I) (Fig. 2, N and O) . In contrast, EK1 exhibited no inhibitory activity against VSV-G-mediated viral infection (Fig. 2P) . The EK1-scrambled peptide showed no inhibitory activity on infection by any of these pseudoviruses (Fig. 2 , I to P). As previously reported (10), we failed to assemble a pseudotyped SHC014 and thus did not perform pseudovirus infection assays on this virus. Collectively, pseudovirus infection by all HCoVs and SL-CoVs could be efficiently blocked by EK1, further indicating that EK1 has broad-spectrum antiviral activity against infection by pan-HCoVs, including -HCoVs, -HCoVs, and SL-CoVs.