Description of CoV-S[1047-1210]
General information on CoV-S [1047-1210]
The spike protein of the new coronavirus strain consists of a variable S1 subunit responsible for binding human ACE2 receptor and a more conserved S2 subunit responsible for membrane fusion. Although the S1 subunit has often been regarded as an attractive target for therapy and vaccine development, the more conserved S2 domain is also referred to as a desirable target for therapies able to confer broad-range protection against multiple strains of coronavirus.
The S2 region becomes exposed after proteolytic cleavage at the furin cleavage site found between residues R685 and S686. The 164 amino acid long domain comprised between residues 1047 and 1210 is located on the tail region of the S2 subunit of protein S of SARS-CoV-2 and it contains the heptad repeat 2 or HR2 (D1163 to E1202).
Like the heptad repeat 1 or HR1, the HR2 is composed of a repetitive heptapeptide (HPPHCPC) containing a mixture of hydrophobic, hydrophilic, and other charged residues. Its composition allows the HR region to adopt an α-helix secondary structure which contains a hydrophobic interface responsible for driving the process of membrane fusion.
The HR1 and HR2 trimers assemble in an antiparallel manner establishing the fusion core (or six-helix bundle). This conformation pulls the viral and the cellular membranes closer so they can fuse, and it brings the fusion protein into a stable post-fusion state.
Previous studies with HIV-1 gp41 showed that HR2-derived peptides could bind to the HR1 region in the prefusion state, preventing it from binding to the real HR2 region and thus prevent the formation of the fusion core. These competitive peptides were able to inhibit HIV-1 infection at nanomolar concentrations. For this reason, since SARS-CoV-2 appears to infect the cells through a similar mechanism, it is worth investigating if the use of HR2-derived peptides or anti-HR2 antibodies could inhibit the infection and consequently arrest the progression of the COVID-19 disease.
|Buffer||PBS, pH7.5, 0.02% NLS|
|Delivery condition||Dry Ice|