Mary Wilson
Well-known member
Published: 02 January 2023
DOI https://doi.org/10.1038/s41422-022-00753-4
Hua Peng & Yang-Xin Fu
New targets for broad-spectrum vaccines are urgently needed to defend the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a recent study in Cell Research, Pang et al. reported a novel variant-proof SARS-CoV-2 vaccine targeting a transient intermediate conformational status of the HR domains in the S2 subunit.
The S2 subunit of spike protein is known to be highly conserved compared to the S1 subunit among different coronaviruses. Thus, a pan-coronavirus fusion inhibitor against the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) would be appreciated for dealing with the future potential variants and sublineages.[SUP]1[/SUP] During cell infection by the SARS-CoV-2 virus, the heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of spike protein S2 region assemble into a six-helix bundle to fuse virus envelope to the host cell membrane, and release viral RNA into the host cell.[SUP]2[/SUP] An S2 subunit structural analysis has shown that mutations do not alter the global architecture of the post-fusion HR1–HR2 bundle in the variants, suggesting that the interfaces between HR1 and HR2 are good targets for developing antiviral inhibitors against most variants of SARS-CoV-2.[SUP]3[/SUP] Synthetic peptides or other inhibitory molecules for blocking the HR transformation are logical approaches to inhibit viral entry to the host cells.[SUP]4,5[/SUP] However, the short half-life of peptides limits their clinical application. Moreover, the S2 conformation is highly dynamic during membrane fusion, presenting a significant challenge in discovering blocking peptides or antibodies against this protein subunit.[SUP]6[/SUP] In this aspect, viral proteins mimicking the intermediate conformation are valuable for designing vaccines targeting the coronavirus S2 protein. Several S2 vaccines have been reported, providing beneficial information.[SUP]7,8[/SUP]
In a study published in Cell Research, the authors have designed and developed a novel SARS-CoV-2 vaccine (HR1–HR2–HR1, HR121 recombinant protein) targeting the HR1 domain present in the fusion intermediate conformation of the S2 subunit of SARS-CoV-2 spike protein.[SUP]9
...
https://www.nature.com/articles/s41422-022-00753-4#citeas[/SUP]
DOI https://doi.org/10.1038/s41422-022-00753-4
Hua Peng & Yang-Xin Fu
New targets for broad-spectrum vaccines are urgently needed to defend the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a recent study in Cell Research, Pang et al. reported a novel variant-proof SARS-CoV-2 vaccine targeting a transient intermediate conformational status of the HR domains in the S2 subunit.
The S2 subunit of spike protein is known to be highly conserved compared to the S1 subunit among different coronaviruses. Thus, a pan-coronavirus fusion inhibitor against the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) would be appreciated for dealing with the future potential variants and sublineages.[SUP]1[/SUP] During cell infection by the SARS-CoV-2 virus, the heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of spike protein S2 region assemble into a six-helix bundle to fuse virus envelope to the host cell membrane, and release viral RNA into the host cell.[SUP]2[/SUP] An S2 subunit structural analysis has shown that mutations do not alter the global architecture of the post-fusion HR1–HR2 bundle in the variants, suggesting that the interfaces between HR1 and HR2 are good targets for developing antiviral inhibitors against most variants of SARS-CoV-2.[SUP]3[/SUP] Synthetic peptides or other inhibitory molecules for blocking the HR transformation are logical approaches to inhibit viral entry to the host cells.[SUP]4,5[/SUP] However, the short half-life of peptides limits their clinical application. Moreover, the S2 conformation is highly dynamic during membrane fusion, presenting a significant challenge in discovering blocking peptides or antibodies against this protein subunit.[SUP]6[/SUP] In this aspect, viral proteins mimicking the intermediate conformation are valuable for designing vaccines targeting the coronavirus S2 protein. Several S2 vaccines have been reported, providing beneficial information.[SUP]7,8[/SUP]
In a study published in Cell Research, the authors have designed and developed a novel SARS-CoV-2 vaccine (HR1–HR2–HR1, HR121 recombinant protein) targeting the HR1 domain present in the fusion intermediate conformation of the S2 subunit of SARS-CoV-2 spike protein.[SUP]9
...
https://www.nature.com/articles/s41422-022-00753-4#citeas[/SUP]