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

To evaluate the prophylactic and therapeutic potentials of EK1 against MERS-CoV infection, we took advantage of the well-characterized transgenic (Tg) mice globally expressing human dipeptidyl peptidase IV (DPP4) viral receptor. We treated mice with 200 g of EK1 or with PBS 30 min before or after challenge with MERS-CoV at 10 4 TCID 50 . Likewise, the weight loss of Tg mice treated with EK1 before or after MERS-CoV challenge was insignificant and rapidly recovered at 16 dpi, while untreated mice progressively lost significant weight before succumbing to infection within 9 dpi with 100% mortality (Fig. 3 , H to J). In contrast, the survival rates in the EK1 prophylactic and therapeutic groups were 100 and 75%, respectively ( Fig. 3 , H to J). When the yield of infectious viruses in lungs was used as the end point for assessing the efficacy of EK-1 on MERS-CoV infection, we were unable to recover any infectious virus from both EK1 prophylactic and therapeutic groups, in sharp contrast to the untreated controls (Fig. 3J ). Together, these results indicated that the peptide EK1 has broad and potent prophylactic and therapeutic efficacy against HCoV infections.