| General information | |
| ACovPid: | ACoVP100066 |
| 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: | Human coronavirus OC43 (HCoV-OC43) : 31631 |
| Inhibition Value Type: | IC50 |
| Inhibitory Effect: | 0.6 |
| Inhibitory Unit: | µM |
| Target Domain Name: | HR1 domain of HCoV-OC43 |
| Assay: | Cytopathic effect assay |
| Assay Description: | The inhibitory activity of peptides against OC43 replication in HCT-8 cells was assessed. Briefly, 100 TCID50 of OC43 was mixed with a test peptide at graded concentration and incubated at 37°C for 30 min. The mixture was then applied in triplicate onto the monolayer of HCT-8 cells grown in a 96-well microtiter plate. On day 5 after infection, viral titer in the culture medium was tested, and TCID50 was calculated on the basis of the cytopathic effect (CPE). |
| Anti-CoV activity in vivo: | In the OC43-infected mouse model, we treated newborn mice with EK1 at a dose of 5 mg/kg or with PBS 30 min before or after challenge with HCoV-OC43 at 102 TCID50 (50% tissue culture infectious dose). Body weight of mice in the viral control group decreased, starting from 5 days postinfection (dpi), and mice succumbed to infection by 10 dpi with 100% mortality (Fig. 3, E to G). In contrast, the final survival rate of mice in the EK1 prophylactic and therapeutic groups was 100 and 66.7%, respectively (Fig. 3E), and their body weight either appeared normal (prophylactic) or rapidly recovered at 16 dpi (therapeutic) (Fig. 3F). Meanwhile, we tested the viral titers in brains of mice of all groups at 5 dpi. Infectious virus was readily detectable in the viral control group, whereas infectious virus titers were below the limit of detection (2 log TCID50/g) in the EK1 prophylactic mice or very low in the EK1 therapeutic mice (Fig. 3G). However, the infectious virus titers in the brains of mice that died during EK1 therapeutic treatment were as high as those in the brains of viral control mice without EK1 treatment, while the viral titers in the brains of survival mice with EK1 therapeutic treatment and in those of normal control mice were both undetectable (fig. S2E). Consistently, the brains of mice that died during EK1 therapeutic treatment exhibited similar histopathological changes as those of the viral control mice, i.e., similar amount of vacuolation, degeneration, and infiltration (fig. S2F). In contrast, the brains of the survival mice with EK1 therapeutic treatment and those of the normal control mice showed no apparent histopathological changes. |
| 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: | |
| Structure Experiment Verified: | NO |
| Similar Peptides: | ACoVP100015 ACoVP100014 ACoVP100013 ACoVP100001 ACoVP100011 |
| Target Domain information | |
| Target Domain Full Name: | Heptad repeat 1 (HR1) domain of Human coronavirus OC43 (HCoV-OC43) spike glycoprotein |
| Target Type: | glycoprotein |
| UniprotID [Sequence]: | P36334 [1004-1054] |
| Target Synonyms: | Alternative name(s) for spike glycoprotein: E2 Peplomer protein S glycoprotein |
| Target Source: | Human coronavirus OC43 (HCoV-OC43) : 31631 |
| Target Structure: | |