Fusion Peptide (EK1) for SARS-CoV-2 Treatment
An outbreak of pneumonia caused by an unknown virus occurred in Wuhan, China in December of 2019. The pathogen was soon identified to be a novel coronavirus, SARS-CoV-2, named by International Committee on Taxonomy of Viruses (ICTV). Previous researches indicated that by introducing negatively and positively charged amino acids Glu (E) and Lys (K), EK1 peptide can potently inhibits multiple CoV cell-cell fusion and blocks various pseudotyped and live CoV infection. Creative Biolabs offers a range of bio-pharmaceutical products. We provide EK1 fusion peptide development services to help you for SARS-CoV-2 researches and treatments and other CoV diseases, such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS).
Pathogenic human coronaviruses (HCoVs) are still major threats to human health, such as in past SARS-CoV and MERS-CoV, and SARS-CoV-2 nowadays. It has reported that coronaviruses are enveloped viruses of which both the receptor binding and the membrane fusion process are mediated via the spike (S) membrane glycoprotein. Fig.1 shows that the functional domains in S protein of SARS-CoV-2. Among the Fig.1, SP means signal peptide; NTD means N-terminal domain; RBD means receptor-binding domain; FP means fusion peptide; HR1 means heptad repeat 1; HR2 means heptad repeat 2; TM means transmembrane domain; CP means cytoplasmic domain.
Fig.1 The representative scheme of functional domains in S protein of 2019-nCoV. (Jiang, 2020)
The S proteins consist of two subunits, S1 and S2, shown in Fig2. The S1 subunit binds the cellular receptor through its RBD, and then conformational changes in the S2 subunit, which makes the fusion peptide insert into the host target cell membrane. HR1 region in the S2 subunit forms a homotrimeric assembly, which exposes three highly conserved hydrophobic grooves on the surface and bind HR2. This six-helix bundle (6-HB) core structure can help the viral and cellular membranes to close proximity in order for viral fusion and entry. Therefore, the S protein is a crucial target for the discovery and development of SARS-CoV-2 drugs and other CoV drugs.
Fig.2 Target sites in S protein of 2019-nCoV for development of vaccines, antibodies and fusion/entry inhibitors. (Jiang, 2020)
Peptides from the HR2 regions of SARS-CoV and MERS-CoV of spike (S) proteins can competitively inhibit viral 6-HB formation, thereby stopping viral fusion and entry into host cells. A modified OC43-HR2P peptide, EK1, is a pan-CoV fusion inhibitor (peptide), which can inhibit infection of five human coronaviruses via inhibiting viral fusion, including SARS-CoV and MERS-CoV, and three bat-SL (SARS-Like)-CoVs. According to last researches, EK1 shows gradually increased solubility and excellent inhibitory activity in cell-cell fusion assays. In vivo studies demonstrated that administration of EK1 by the nasal route indicates highly protective effects and safety profiles, proving its clinical potential. Besides, structural studies of EK1 in complex with HR1s from different HCoVs explain the conserved basis for the HR1-EK1 interaction and also suggest its potential prophylactic and therapeutic effect against SARS-CoV-2 infection.
At Creative Biolabs, we provide fusion peptide EK1 development services to support the researches of SARS-CoV-2. Creative Biolabs also offers efficient and high-quality antiviral peptide discovery services for our customers. If you want to know more information about EK1 fusion inhibitor (peptide), please feel free to contact us.
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