General information
    ACovPid:ACoVP100001
    Trivial Name:EK1C4
    Amino Acids Sequence:SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKELGSGSG-PEG4-Chol
    Length:41
    C-Terminal Modification:Chol: cholesterol;  
    N-Terminal Modification:None
    Chemical Modification:PEG4: polyethylene glycol 4-based spacer;  
    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,and EK1C4 was the optimized form of EK1.
    Against Virus:

    Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2) : 2697049

    Inhibition Value Type:IC50
    Inhibitory Effect:0.0365
    Inhibitory Unit:µM
    Target Domain Name:HR1 domain of SARS-CoV-2
    Assay:Plaque reduction assay
    Assay Description:Inhibition activity of peptides on SARS-CoV-2 was determined by plaque reduction assay. Peptides with different dilution concentrations were mixed with SARS-CoV-2 (100 TCID50) for 30 min and then added to monolayer VERO-E6 cells. After adsorption at 37 °C, the supernatant was removed, and 0.9% methyl cellulose was overlaid on the cells. After 72 h, the plates were fixed and stained. Plaques were counted by fixing with 4% paraformaldehyde and staining with 0.1% crystal violet.
    Anti-CoV activity in vivo:We used an HCoV-OC43 infection mouse model to further investigate the potential prophylactic effect of EK1C4 in clinical applications via the intranasal administration route (Fig. 6f, g). In the OC43-infected mouse model, we treated newborn mice with EK1C4 at a single dose of 0.5 mg/kg 0.5 h (Pre-0.5), 2 h (Pre-2), 4 h (Pre-4), 12 (Pre-12) and 24 h (Pre-24) before challenging with HCoV-OC43 at 100 TCID50 (50% tissue culture infectious dose). Starting from 4 days’ post-infection (dpi), the body weight of mice in the viral control group decreased significantly along with 100% mortality (Fig. 6f, g). The final survival rates of mice in Pre-0.5, Pre-2, Pre-4, Pre-12 and Pre-24 groups were 100%, 100%, 100%, 83 and 0%, respectively (Fig. 6f, g). In contrast, EK1 with a single dose of 20 mg/kg via nasal administration exhibited very promising prophylactic effect in the Pre-0.5 h and Pre-1 h groups, whereas all mice in the EK1-Pre-2 h group eventually died similarly to the mice in the viral control group (Supplementary information, Fig. S5). These results suggested that EK1C4 has better stability, antiviral activity, and prolonged half-life in the airway environment when compared with EK1. We then tested the therapeutic effect of EK1C4 0.5 h (Post-0.5 group) and 2 h (Post-2 group) after HCoV-OC43 infection (Fig. 6h, i). The Post-0.5 group and Post-2 group mice showed 100% and 16.7% survival rate, respectively, suggesting that EK1C4 harbors good therapeutic effect after a short period of HCoV-OC43 infection, possibly resulting from the establishment of HCoVOC43 infection in mouse brain where EK1C4 cannot get through the blood brain barrier via nasal administration.14 As shown in Supplementary information, Fig. S6, high viral titer was detected in brains of all 5 mice in Pre-24 group and 4 out of 5 mice in Post-2 group, but was not detected in brain tissues of all mice in Pre-0.5, Pre-2, Pre-4, and Post-0.5 groups, while only moderate level of viral titer was detected in brain tissue in one of the 5 mice in Pre- 12 group (Supplementary information, Fig. S6a, b). Similar to those in the viral control mice, mice in Pre-24 and Post-2 groups exhibited similar histopathological changes in brain tissues, including vacuolation, degeneration, and infiltration. However, the brain tissues of mice in Pre-0.5, Pre-2, Pre-4, Pre-12 and Post- 0.5 group as well as the normal control group showed no apparent histopathological changes (Supplementary information, Fig. S6c).
    Reference:32231345
    Comment:EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.
    3D structure:

    Structure Experiment Verified:
    Similar Peptides:ACoVP100011   ACoVP100010   ACoVP100009   ACoVP100008   ACoVP100007

    Target Domain information
    Target Domain Full Name:Heptad repeat 1 (HR1) domain of Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2) spike glycoprotein
    Target Type:glycoprotein
    UniprotID [Sequence]:

    P0DTC2 [920-970]

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

    Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2) : 2697049

    Target Structure:6LVN, 6LXT, 6LZG, 6M0J, 6M17, 6M1V, 6VSB, 6VW1, 6VXX, 6VYB, 6W41, 6WPS, 6WPT, 6X29, 6X2A, 6X2B, 6X2C, 6X6P, 6X79, 6XC2, 6XC3, 6XC4, 6XC7, 6XCM, 6XCN, 6XDG, 6XE1, 6XEY, 6XF5, 6XF6, 6XKL, 6XKP, 6XKQ, 6XLU, 6XM0, 6XM3, 6XM4, 6XM5, 6XR8, 6XRA, 6XS6, 6YLA, 6YM0, 6YOR, 6YZ5, 6YZ7, 6Z2M, 6Z43, 6Z97, 6ZB4, 6ZB5, 6ZBP, 6ZCZ, 6ZDG, 6ZDH, 6ZER, 6ZFO, 6ZGE, 6ZGG, 6ZGI, 6ZH9, 6ZHD, 6ZLR, 6ZOW, 6ZOX, 6ZOY, 6ZOZ, 6ZP0, 6ZP1, 6ZP2, 6ZP5, 6ZP7, 6ZWV, 6ZXN, 7A25, 7A29, 7A4N, 7A5R, 7A5S, 7A91, 7A92, 7A93, 7A94, 7A95, 7A96, 7A97, 7A98, 7AD1, 7BWJ, 7BYR, 7BZ5, 7C01, 7C2L, 7C8D, 7C8V, 7C8W, 7CAB, 7CAH, 7CAI, 7CAK, 7CAN, 7CDI, 7CDJ, 7CH4, 7CH5, 7CHB, 7CHC, 7CHE, 7CHF, 7CHH, 7CJF, 7CN9, 7CT5, 7CWM, 7CWN, 7CWO, 7CWS, 7CWU, 7DCC, 7DCX, 7DD2, 7DD8, 7DDD, 7DDN, 7DF3, 7DF4, 7DK3, 7DK4, 7DK5, 7DK6, 7DK7, 7DMU, 7JJC, 7JJI, 7JJJ, 7JMO, 7JMP, 7JMW, 7JV2, 7JV4, 7JV6, 7JVA, 7JVB, 7JVC, 7JW0, 7JWB, 7JWY, 7JX3, 7JZL, 7JZM, 7JZN, 7JZU, 7K43, 7K45, 7K4N, 7K8M, 7K8S, 7K8T, 7K8U, 7K8V, 7K8W, 7K8X, 7K8Y, 7K8Z, 7K90, 7K9Z, 7KDG, 7KDH, 7KDI, 7KDJ, 7KDK, 7KDL, 7KE4, 7KE6, 7KE7, 7KE8, 7KE9, 7KEA, 7KEB, 7KEC, 7KJ2, 7KJ3, 7KJ4, 7KJ5, 7KKK, 7KKL, 7KL9, 7KMB, 7KMS, 7KMZ, 7KNB, 7KNE, 7KNH, 7KNI, 7L02, 7L06, 7L09