Middle East respiratory syndrome coronavirus (MERS-CoV), capable of zoonotic transmission, has been associated with emerging viral pneumonia in humans. In this study, a set of highly potent peptides were designed to prevent MERS-CoV fusion through competition with heptad repeat domain 2 (HR2) at its HR1 binding site. We designed eleven peptides with stronger estimated HR1 binding affinities than the wild-type peptide to prevent viral fusion with the cell membrane. Eight peptides showed strong inhibition of spike-mediated MERS-CoV cell-cell fusion with IC50 values in the nanomolar range (0.25–2.3 µM). Peptides #4–6 inhibited 95–98.3% of MERS-CoV plaque formation. Notably, peptide four showed strong inhibition of MERS-CoV plaques formation with EC50 = 0.302 µM. All peptides demonstrated safe profiles without cytotoxicity up to a concentration of 10 μM, and this cellular safety, combined with their anti-MERS-CoV antiviral activity, indicate all peptides can be regarded as potential promising antiviral agents.
【저자키워드】 coronavirus, Drug discovery, antivirals, MERS-CoV, fusion inhibitors, 【초록키워드】 peptide, cytotoxicity, antiviral activity, IC50, binding affinity, binding site, Viral pneumonia, humans, Antiviral agents, cell-cell fusion, cellular, Concentration, Safe, Middle East, profile, domain, wild-type, zoonotic transmission, respiratory syndrome coronavirus, plaque, cell membrane, EC50, heptad repeat, Prevent, inhibited, demonstrated, 【제목키워드】 CoV, fusion, potent, New,