Compound class: Peptide or derivative

Comment: EK-1 is a synthetic peptide whose sequence was derived from the heptad repeat (HR) domain of the S2 subunit of the spike protein of human coronavirus (hCoV) OC43 [3]. It interacts with the spike protein's HR1 domain and blocks the conformational changes in spike that are essential for viral fusion with the host cell membrane. EK-1 therefore acts as a functional fusion inhibitor. The spike HR1 domain is conserved among various hCoVs (MERS-CoV, SARS-CoV, CoV-OC43) making this a suitable target for the development of pan-CoV therapeutics, against existing pathogenic hCoVs, and against novel strains that are likely to emerge in the future. EK-1 has been proposed as such a pan-CoV viral fusion inhibitor based on experimental evidence [3]. EK-1 was developed prior to the emergence of SARS-CoV-2 in 2019. A study published in 2021 reported that EK-1 (and a modified lipidated version EK-1-C4 [2]) inhibited infection by the B.1.351 and P.1 CoV-2 variants which arose during the SARS-CoV-2 pandemic and that are insensitive to neutralising antibodies (escape variants), including some of those that have been approved for clinical use [1].