ArticleEmerging microbes & infections2022
An engineered 5-helix bundle derived from SARS-CoV-2 S2 pre-binds sarbecoviral spike at both serological- and endosomal-pH to inhibit virus entry.
Article in Emerging microbes & infections, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 17 citations in OpenAlex.
- High throughput screening for SARS-CoV-2 inhibitors targeting 5 helix bundle.SLAS discovery : advancing life sciences R & D · 2025Article
- Structural basis and mode of action for two broadly neutralizing nanobodies targeting the highly conserved spike stem-helix of sarbecoviruses including SARS-CoV-2 and its variants.PLoS pathogens · 2025Article
- Research Progress on Spike-Dependent SARS-CoV-2 Fusion Inhibitors and Small Molecules Targeting the S2 Subunit of Spike.Viruses · 2024Review
- Clinical development of antivirals against SARS-CoV-2 and its variants.Current research in microbial sciences · 2024Review
- HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitorActa pharmaceutica Sinica. B · 2023Article
- Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines.Signal transduction and targeted therapy · 2023Review
- Towards developing a variant-proof SARS-CoV-2 vaccine.Cell research · 2023Article
- Potent inhibition of diverse Omicron sublineages by SARS-CoV-2 fusion-inhibitory lipopeptides.Antiviral research · 2022Article
- SP-A binding to the SARS-CoV-2 spike protein using hybrid quantum and classical in silico modeling and molecular pruning by Quantum Approximate Optimization Algorithm (QAOA) Based MaxCut with ZDOCK.Frontiers in immunology · 2022Article
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Authors and funding
20 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related sarbecoviruses enter host cells by receptor-recognition and membrane-fusion. An indispensable step in fusion is the formation of 6-helix bundle by viral spike heptad repeats 1 and 2 (HR1 and HR2). Here, we report the construction of 5-helix bundle (5HB) proteins for virus infection inhibition. The optimal construct inhibits SARS-CoV-2 pseudovirus entry with sub-micromolar IC50. Unlike HR2-based peptides that cannot bind spike in the pre-fusion conformation, 5HB features with the capability of binding to pre-fusion spike. Furthermore, 5HB binds viral HR2 at both serological- and endosomal-pH, highlighting its entry-inhibition capacity when SARS-CoV-2 enters via either cell membrane fusion or endosomal route. Finally, we show that 5HB could neutralize S-mediated entry of the predominant SARS-CoV-2 variants and a wide spectrum of sarbecoviruses. These data provide proof-of-concept evidence that 5HB might be developed for the prevention and treatment of SARS-CoV-2 and other emerging sarbecovirus infections.
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