EK-1

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Ligands
EK-1

GtoPdb Ligand ID: 11500

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].

Bioactivity Comments
In cellular infection assays, EK-1 has potent pan-CoV antiviral fusion activity (IC₅₀s 0.19-0.62 μM) [3]. IC₅₀ in a MERS-CoV pseudovirus assay is 0.26 μM, and for SARS-CoV pseudovirus infection the IC₅₀ is 2.23 μM. The specificity of the EK-1 effect was determined using an EK1-scrambled peptide which was inactive in the same assays. Intranasally delivered EK-1 distributes throughout the respiratory tract in mice, is enriched in the lung, and can be detected in liver, kidney, and spleen which is indicative of systemic exposure [3]. This method of administration provides broad anti-hCoV activity in vivo.

Bioactivity Comments

In cellular infection assays, EK-1 has potent pan-CoV antiviral fusion activity (IC₅₀s 0.19-0.62 μM) [3]. IC₅₀ in a MERS-CoV pseudovirus assay is 0.26 μM, and for SARS-CoV pseudovirus infection the IC₅₀ is 2.23 μM. The specificity of the EK-1 effect was determined using an EK1-scrambled peptide which was inactive in the same assays. Intranasally delivered EK-1 distributes throughout the respiratory tract in mice, is enriched in the lung, and can be detected in liver, kidney, and spleen which is indicative of systemic exposure [3]. This method of administration provides broad anti-hCoV activity in vivo.

Selectivity at other protein targets

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Target			Sp.	Type	Action	Value	Parameter	Concentration range (M)	Reference
CoV Spike glycoprotein			SARS-CoV	Inhibitor	Binding	-	-	-	3
⤷	[3]