EK1C4 - Pan-Coronavirus Fusion Inhibitor

Lipopeptide-based SARS-CoV-2 fusion inhibitor

EK1C4 is a lipopeptide that potently inhibits SARS-CoV-2 (and other human coronaviruses, HCoV) fusion with target cells [1]. It is derived from the EK1 peptide to which cholesterol has been covalently attached in the C-terminal, with the help of a flexible polyethylene glycol (PEG) spacer [1].

Mode of action:

EK1C4 binds to a region of the virus Spike (S) protein that is crucial for fusion with the target cell. EK1C4, like EK1, interacts with the heptad repeat domain 1 (HR1) in the S2 subunit of the Spike protein [1,2]. These inhibitors prevent the HR1 and HR2 trimer association to form a six-helix bundle (6-HB) which brings the viral and target cell membranes in close proximity for fusion. EK1C4 has been described as the most potent HCoV fusion/entry inhibitor among EK1 and EK1-derived molecules in cellular assays using pseudotyped or live coronaviruses [1]. It has been suggested that the cholesterol group improves the anti-viral activity of EK1C4, possibly through anchoring the inhibitor to the target membrane, or binding to the hydrophobic groove on HR1 trimers [1]. Intranasally applied EK1C4 protects mice against HCoV-OC43 infection [1]. This lipopeptide has thus the potential to be developed as a pan-coronavirus prophylactic or therapeutic, alone or in combination with neutralizing anti-Spike antibodies.

More details

Key features:

• Potent inhibitor of HCoV fusion/infection of target cells
• InvitroFit™ grade: highly pure (≥95%) and inhibitory function validated in cellular assays

Learn more about InvivoGen's cell fusion assays

References

1. Xia, S et al., 2020. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Research. 30(4):343-355.
2. Xia, S et al., 2020. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell Mol. Immunol. 17:765-767.