ArticleCell discovery2022
A novel cyclic γ-AApeptide-based long-acting pan-coronavirus fusion inhibitor with potential oral bioavailability by targeting two sites in spike protein.
Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The trial behind it
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting Middle East Respiratory Syndrome Coronavirus Spike Fusion Machinery With Antiviral Peptides: In Silico Exploration of the Heptad Repeat 2 Domain.MicrobiologyOpen · 2026Article
- α/Sulfonyl-γ-AApeptide foldamers mitigate Alzheimer's disease pathology by stabilizing transient helical domains in Aβ.Nature communications · 2026Article
- MERS-related coronavirus circulating in pangolins exhibits strong fusogenicity in human cells and high sensitivity to fusion inhibitors.Cell reports. Medicine · 2025Article
- Natural and Designed Cyclic Peptides as Potential Antiviral Drugs to Combat Future Coronavirus Outbreaks.Molecules (Basel, Switzerland) · 2025Review
- Utilizing HCoV-OC43 to better understand the neurological impact of COVID-19.Brain, behavior, & immunity - health · 2024Article
- Article
- Differentiating Cell Entry Potentials of SARS-CoV-2 Omicron Subvariants on Human Lung Epithelium Cells.Viruses · 2024Article
- FEOpti-ACVP: identification of novel anti-coronavirus peptide sequences based on feature engineering and optimization.Briefings in bioinformatics · 2024Article
- 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
- SARS-CoV-2 Omicron subvariants exhibit distinct fusogenicity, but similar sensitivity, to pan-CoV fusion inhibitors.Emerging microbes & infections · 2023Article
- Development of the Safe and Broad-Spectrum Aldehyde and Ketoamide Mpro inhibitors Derived from the Constrained α, γ-AA Peptide Scaffold.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- An inducible hACE2 transgenic mouse model recapitulates SARS-CoV-2 infection and pathogenesis in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- An HR2-Mimicking Sulfonyl-γ-AApeptide Is a Potent Pan-coronavirus Fusion Inhibitor with Strong Blood-Brain Barrier Permeability, Long Half-Life, and Promising Oral Bioavailability.ACS central science · 2023Article
- The discovery of cyclic γ-AApeptides as the promising ligands targeting EP2.Bioorganic & medicinal chemistry letters · 2023Article
- Current state-of-the-art and potential future therapeutic drugs against COVID-19.Frontiers in cell and developmental biology · 2023Review
- Pan-coronavirus fusion inhibitors to combat COVID-19 and other emerging coronavirus infectious diseases.Journal of medical virology · 2023Review
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The receptor-binding domain (RBD) in S1 subunit and heptad repeat 1 (HR1) domain in S2 subunit of SARS-CoV-2 spike (S) protein are the targets of neutralizing antibodies (nAbs) and pan-coronavirus (CoV) fusion inhibitory peptides, respectively. However, neither nAb- nor peptide-based drugs can be used orally. In this study, we screened a one-bead-two-compound (OBTC) cyclic γ-AApeptide library against SARS-CoV-2 S protein and identified a hit: S-20 with potent membrane fusion inhibitory activity, but moderate selectivity index (SI). After modification, one derivative, S-20-1, exhibited improved fusion inhibitory activity and SI (>1000). S-20-1 could effectively inhibit infection by pseudotyped and authentic SARS-CoV-2 and pseudotyped variants of concern (VOCs), including B.1.617.2 (Delta) and B.1.1.529 (Omicron), as well as MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. It could also inhibit infection of a pseudotyped SARS-related coronavirus WIV1 (SARSr-CoV-WIV1) from bats. Intranasal application of S-20-1 to mice before or after challenge with HCoV-OC43 or SARS-CoV-2 provided significant protection from infection. Importantly, S-20-1 was highly resistant to proteolytic degradation, had long half-life, and possessed favorable oral bioavailability. Mechanistic studies suggest that S-20-1 binds with high affinity to RBD in S1 and HR1 domain in S2 of SARS-CoV-2 S protein. Thus, with its pan-CoV fusion and entry inhibitory activity by targeting two sites in S protein, desirable half-life, and promising oral bioavailability, S-20-1 is a potential candidate for further development as a novel therapeutic and prophylactic drug against infection by SARS-CoV-2 and its variants, as well as future emerging and reemerging CoVs.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.