ArticleCell discovery2022
A bispecific nanobody dimer broadly neutralizes SARS-CoV-1 & 2 variants of concern and offers substantial protection against Omicron via low-dose intranasal administration.
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 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- ACE2-fused nanobody targeting a cryptic RBD epitope broadly neutralizes SARS-like viruses.Journal of virology · 2026Article
- Engineered IgA-Fc fusion protein with bioactive nanobody neutralizes SARS-CoV-2 variants with mucosal delivery potential.The Journal of biological chemistry · 2026Article
- Review
- Protein Engineering and Drug Discovery: Importance, Methodologies, Challenges, and Prospects.Biomolecules · 2025Review
- Development of broadly neutralizing antibodies against Omicron variants from existing neutralizing antibodies in clinical trials.Virology journal · 2025Article
- Intranasal delivery of engineered anti-SARS-CoV-2 extracellular vesicles therapeutically represses lung infection and inflammation.Drug delivery and translational research · 2025Article
- Research Progress on the Application of Neutralizing Nanobodies in the Prevention and Treatment of Viral Infections.Microorganisms · 2025Review
- A potent protective bispecific nanobody targeting Herpes simplex virus gD reveals vulnerable epitope for neutralizing.Nature communications · 2025Article
- Potent bivalent nanobody constructs that protect against the SARS-CoV-2 XBB variant.Npj viruses · 2025Article
- A bivalent spike-targeting nanobody with anti-sarbecovirus activity.Journal of nanobiotechnology · 2025Article
- Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control.Signal transduction and targeted therapy · 2024Review
- A review on camelid nanobodies with potential application in veterinary medicine.Veterinary research communications · 2024Review
- Current development of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies (Review).Molecular medicine reports · 2024Review
- Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses.Journal of nanobiotechnology · 2024Review
- Function and mechanism of bispecific antibodies targeting SARS-CoV-2.Cell insight · 2024Review
- Serial Llama Immunization with Various SARS-CoV-2 RBD Variants Induces Broad Spectrum Virus-Neutralizing Nanobodies.Vaccines · 2024Article
- Article
- Application and Method of Surface Plasmon Resonance Technology in the Preparation and Characterization of Biomedical Nanoparticle Materials.International journal of nanomedicine · 2024Review
- Respiratory delivery of passive immunotherapies for SARS-CoV-2 prophylaxis and therapy.Human vaccines & immunotherapeutics · 2023Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Current SARS-CoV-2 Omicron subvariants impose a heavy burden on global health systems by evading immunity from most developed neutralizing antibodies and vaccines. Here, we identified a nanobody (aSA3) that strongly cross-reacts with the receptor binding domain (RBD) of both SARS-CoV-1 and wild-type (WT) SARS-CoV-2. The dimeric construct of aSA3 (aSA3-Fc) tightly binds and potently neutralizes both SARS-CoV-1 and WT SARS-CoV-2. Based on X-ray crystallography, we engineered a bispecific nanobody dimer (2-3-Fc) by fusing aSA3-Fc to aRBD-2, a previously identified broad-spectrum nanobody targeting an RBD epitope distinct from aSA3. 2-3-Fc exhibits single-digit ng/mL neutralizing potency against all major variants of concerns including BA.5. In hamsters, a single systemic dose of 2-3-Fc at 10 mg/kg conferred substantial efficacy against Omicron infection. More importantly, even at three low doses of 0.5 mg/kg, 2-3-Fc prophylactically administered through the intranasal route drastically reduced viral RNA loads and completely eliminated infectious Omicron particles in the trachea and lungs. Finally, we discovered that 2(Y29G)-3-Fc containing a Y29G substitution in aRBD-2 showed better activity than 2-3-Fc in neutralizing BA.2.75, a recent Omicron subvariant that emerged in India. This study expands the arsenal against SARS-CoV-1, provides potential therapeutic and prophylactic candidates that fully cover major SARS-CoV-2 variants, and may offer a simple preventive approach against Omicron and its subvariants.
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.