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 respiratory tract is the primary target tissue of HCoV infection. To investigate the preclinical potential of the EK1 peptide, we administered it via an intranasal route and assessed its distribution within the respiratory tract. We observed the fluorescent signals of Cy5-EK1 mainly in the upper and lower respiratory tract of mice (Fig. 3 , A and B). Compared with those from PBS-treated mice, the lungs obtained from Cy5-EK1-treated mice exhibited significantly higher fluorescence signals (P < 0.0001, n = 3) (Fig. 3 , C and D). Together, these results suggest that EK1 (intranasal) can widely be distributed in the whole respiratory tract and be enriched in the lung. We also noted that Cy5-EK1 administered intranasally could be detected in significant amounts in several extrapulmonary organs, including the liver, kidney, and spleen, in some animals, suggesting that EK1 could enter into the blood circulation and other organs (fig. S3, A and B). This observation suggests that intranasal administration of EK1 could also be beneficial for multiorgan infection or systemic infection of HCoVs, both of which are common in MERS-CoV infection.