Discovery of New Potent anti-MERS CoV Fusion Inhibitors

• Main Authors: Mahmoud Kandeel (Author), Mizuki Yamamoto (Author), Byoung Kwon Park (Author), Abdulla Al-Taher (Author), Aya Watanabe (Author), Jin Gohda (Author), Yasushi Kawaguchi (Author), Kentaro Oh-hashi (Author), Hyung-Joo Kwon (Author), Jun-ichiro Inoue (Author)
• Format: Book
• Published: Frontiers Media S.A., 2021-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1663-9812
10.3389/fphar.2021.685161