Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4

The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability. Moreover, these peptides, particularly HKU4-HR2P2 and HKU4-HR2P3, exhibited potent inhibitory activity against MERS-CoV S-mediated cell–cell fusion and viral infection, suggesting that these HKU4 HR2-derived peptides could be candidates for futher development as antiviral agents against MERS-CoV infection.