AUTHOR=Kandeel Mahmoud , Yamamoto Mizuki , Park Byoung Kwon , Al-Taher Abdulla , Watanabe Aya , Gohda Jin , Kawaguchi Yasushi , Oh-hashi Kentaro , Kwon Hyung-Joo , Inoue Jun-ichiro TITLE=Discovery of New Potent anti-MERS CoV Fusion Inhibitors JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.685161 DOI=10.3389/fphar.2021.685161 ISSN=1663-9812 ABSTRACT=

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.