ArticleActa pharmaceutica Sinica. B2023
HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor
Article in Acta pharmaceutica Sinica. B, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Receptor binding domain-independent pancoronavirus vaccine design by fusion of conserved T/B Epitopes.Emerging microbes & infections · 2026Article
- An Engineered HR1-Stem Helix-HR2 Trimeric Platform for Developing Broad-Spectrum Coronavirus Vaccines.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A novel fusion protein of COVID-19 virus enhancing protection of Syrian hamsters infected with SARS-CoV-2.Acta pharmaceutica Sinica. B · 2026Article
- Characterization and immunogenicity of nanoparticle vaccines based on Clade 2 and Clade 3 sarbecovirus S2 proteins.NPJ vaccines · 2025Article
- Yeast-two-hybrid based high-throughput screening to discover SARS-CoV-2 fusion inhibitors by targeting the HR1/HR2 interaction.Acta pharmaceutica Sinica. B · 2025Article
- Merbecovirus S2 subunit vaccines elicit cross reactive antibodies and provide partial protection against MERS coronavirus.Npj viruses · 2025Article
- Review
- Targeting heptad repeats and fusion peptide: nanoparticle vaccine elicits mucosal immune response against SARS-CoV-2 variants.Journal of nanobiotechnology · 2025Article
- Review
- Identification ofMolecules (Basel, Switzerland) · 2025Article
- Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice.Nature communications · 2025Article
- Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models.Zoological research · 2024Review
- An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen.Emerging microbes & infections · 2023Article
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The continuously emerging SARS-CoV-2 variants pose a great challenge to the efficacy of current drugs, this necessitates the development of broad-spectrum antiviral drugs. In the previous study, we designed a recombinant protein, heptad repeat (HR) 121, as a variant-proof vaccine. Here, we found it can act as a fusion inhibitor and demonstrated broadly neutralizing activities against SARS-CoV-2 and its main variants. Structure analysis suggested that HR121 targets the HR2 domain in SARS-CoV-2 spike (S) 2 subunit to block virus-cell fusion. Functional experiments demonstrated that HR121 can bind HR2 at serological-pH and endosomal-pH, highlighting its inhibition capacity when SARS-CoV-2 enters via either cellular membrane fusion or endosomal route. Importantly, HR121 can effectively inhibit SARS-CoV-2 and Omicron variant pseudoviruses entering the cells, as well as block authentic SARS-CoV-2 and Omicron BA.2 replications in human pulmonary alveolar epithelial cells. After intranasal administration to Syrian golden hamsters, it can protect hamsters from SARS-CoV-2 and Omicron BA.2 infection. Together, our results suggest that HR121 is a potent drug candidate with broadly neutralizing activities against SARS-CoV-2 and its variants.
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