General information
    ACovPid:ACoVP100065
    Trivial Name:EK1
    Amino Acids Sequence:SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL
    Length:36
    C-Terminal Modification:None
    N-Terminal Modification:None
    Chemical Modification:None
    Peptide Source:

    Human coronavirus OC43 (HCoV-OC43) : 31631

    Source Description:Peptide OC43-HR2P was derived from the HR2 domain of HCoV-OC43. EK1 was the optimized form of OC43-HR2P.
    Against Virus:

    Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1) : 1263720

    Inhibition Value Type:IC50
    Inhibitory Effect:0.11
    Inhibitory Unit:µM
    Target Domain Name:HR1 domain of MERS-CoV (Betacoronavirus England 1)
    Assay:Cytopathic effect assay
    Assay Description:The inhibitory activity of peptide against MERS-CoV replication was tested in Calu-3 cells. Briefly, 60 µl of a serially twofold diluted peptide was incubated with 60 µl (120 TCID50) of MERS-CoV in MEM medium supplemented with 2% FBS (M-2 medium) in duplicate wells of 96-well plates for ~60 min at room temperature. One hundred microliters of the peptide/MERSCoV mixtures was then transferred into confluent Calu-3 cells grown in 96-well plates. Wells of Calu-3 cells cultured with M-2 medium with and without virus were included in these assays as positive and negative controls, respectively. While the advanced CPE of Calu-3 cells could develop within 24 to 36 hours in response to MERS-CoV infection at higher multiplicities of infection (MOIs) of 1 or 0.1, we did not observe any prominent formation of CPE until ~ 60 to 72 hours after infection at an estimated MOI of ~ 0.001. Hence, to more accurately measure the efficacy of peptide inhibitors against MERS-CoV infection, we harvested the supernatants at 72 hours and quantified infectious virus titers by the standard Vero E6–based infectivity assays and expressed the titers as log10 TCID50/ml.
    Anti-CoV activity in vivo:To evaluate the prophylactic and therapeutic potentials of EK1 against MERS-CoV infection, we took advantage of the well-characterized transgenic (Tg) mice globally expressing human dipeptidyl peptidase IV (DPP4) viral receptor. We treated mice with 200 µg of EK1 or with PBS 30 min before or after challenge with MERS-CoV at 104 TCID50. Likewise, the weight loss of Tg mice treated with EK1 before or after MERS-CoV challenge was insignificant and rapidly recovered at 16 dpi, while untreated mice progressively lost significant weight before succumbing to infection within 9 dpi with 100% mortality (Fig. 3, H to J). In contrast, the survival rates in the EK1 prophylactic and therapeutic groups were 100 and 75%, respectively (Fig. 3, H to J). When the yield of infectious viruses in lungs was used as the end point for assessing the efficacy of EK-1 on MERSCoV infection, we were unable to recover any infectious virus from both EK1 prophylactic and therapeutic groups, in sharp contrast to the untreated controls (Fig. 3J).
    Reference:30989115
    Comment:We found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short-HCoV and long-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.
    3D structure:

    StructureACoVP100065

    Structure Experiment Verified:NO
    Similar Peptides:ACoVP100015   ACoVP100014   ACoVP100013   ACoVP100001   ACoVP100011

    Target Domain information
    Target Domain Full Name:Heptad repeat 1 (HR1) domain of Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1) spike glycoprotein
    Target Type:glycoprotein
    UniprotID [Sequence]:

    K9N5Q8 [994-1044]

    Target Synonyms:Alternative name(s) for spike glycoprotein: E2 Peplomer protein S glycoprotein
    Target Source:

    Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1) : 1263720

    Target Structure:4L72, 4MOD, 4XAK, 4ZPT, 4ZPV, 4ZPW, 5GMQ, 5GR7, 5GSB, 5GSR, 5GSV, 5GSX, 5VYH, 5W9H, 5W9I, 5W9J, 5W9K, 5W9L, 5W9M, 5W9N, 5W9O, 5W9P, 5X4R, 5X59, 5X5C, 5X5F, 5YY5, 5ZVK, 5ZXV, 6C6Y, 6C6Z, 6J11, 6J2J, 6L8Q, 6PXH, 6WAR