Antibody-like proteins that capture and neutralize SARS-CoV-2

Kondo, Tohru; Iwatani, Yoshinori; Matsuoka, Katsunari; Fujino, Tomoshige; Umemoto, Shun; Yokomaku, Yoshiyuki; Ishizaki, K.; Kito, Seita; Sezaki, T; Hayashi, Gosuke; Murakami, Hiroshi

doi:10.1126/sciadv.abd3916

Cited by 50 publications

(70 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another example of nanobody library is that it can be constructed from a llama immunized with the recombinant RBD, and this library was selected using a proteomic strategy to achieve anti-RBD nanobodies with picomolar to femtomolar affinity [ 62 ]. Apart from the nanobody, the monobody library can be synthetically constructed and screened against the SARS-CoV-2 S1 subunit, resulting in anti-S1 monobodies with sub-nanomolar to nanomolar affinity [ 63 ]. These monobodies were then applied to capture SARS-CoV-2 particles from the nasal swab samples of patients.…”

Section: Sars-cov-2 Biomarkers and Biorecognition Elementsmentioning

confidence: 99%

“…HRP is horseradish peroxidase enzyme that is used to amplify signal in photometric assays by catalyzing the conversion chemiluminescent substrates. Adapted from [ 63 ], Copyright, The Authors, some rights reserved; exclusive licensee AAAS. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC) …”

Section: Recent Biosensing Approaches For Detecting Sars-cov-2mentioning

confidence: 99%

“…For example, the recently engineered monobodies, which specifically bind to the S1 subunit of SARS-CoV-2, were used in ELISA assay, and the result was comparable as using antibody (Fig. 4b ) [ 63 ]. These monobodies can be also coated on the magnetic beads to pull down and enrich SARS-CoV-2 virus particles from patient nasal swab samples for RT-PCR.…”

Section: Recent Biosensing Approaches For Detecting Sars-cov-2mentioning

confidence: 99%

See 2 more Smart Citations

Advances in emergent biological recognition elements and bioelectronics for diagnosing COVID-19

et al. 2021

View full text Add to dashboard Cite

Coronaviruses pose a serious threat to public health. Tremendous efforts are dedicated to advance reliable and effective detection of coronaviruses. Currently, the coronavirus disease 2019 (COVID-19) diagnosis mainly relies on the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic materials by using reverse transcription-polymerase chain reaction (RT-PCR) assay. However, simpler and more rapid and reliable alternatives are needed to meet high demand during the pandemic. Biosensor-based diagnosis approaches become alternatives for selectively and rapidly detecting virus particles because of their biorecognition elements consisting of biomaterials that are specific to virus biomarkers. Here, we summarize biorecognition materials, including antibodies and antibody-like molecules, that are designed to recognize SARS-CoV-2 biomarkers and the advances of recently developed biosensors for COVID-19 diagnosis. The design of biorecognition materials or layers is crucial to maximize biosensing performances, such as high selectivity and sensitivity of virus detection. Additionally, the recent representative achievements in developing bioelectronics for sensing coronavirus are included. This review includes scholarly articles, mainly published in 2020 and early 2021. In addition to capturing the fast development in the fields of applied materials and biodiagnosis, the outlook of this rapidly evolving technology is summarized. Early diagnosis of COVID-19 could help prevent the spread of this contagious disease and provide significant information to medical teams to treat patients.

show abstract

Section: Sars-cov-2 Biomarkers and Biorecognition Elementsmentioning

confidence: 99%

Section: Recent Biosensing Approaches For Detecting Sars-cov-2mentioning

confidence: 99%

Section: Recent Biosensing Approaches For Detecting Sars-cov-2mentioning

confidence: 99%

See 1 more Smart Citation

Advances in emergent biological recognition elements and bioelectronics for diagnosing COVID-19

et al. 2021

View full text Add to dashboard Cite

show abstract

“…For example, one study found that none of the 206 RBD-specific monoclonal antibodies derived from single B cells of eight SARS-CoV-2 infected individuals cross-reacted with SARS-CoV or MERS-CoV RBDs (23). Antibody-like monobodies designed to bound to the SARS-CoV-2 S protein also did not bind that of SARS-CoV (24). As a further complicating factor, RNA viruses accumulate mutations over time, which yields antibody resistance and requires the use of antibody cocktails to avoid mutational escape (25).…”

Section: Introductionmentioning

confidence: 99%

Small-MoleculeIn VitroInhibitors of the Coronavirus Spike – ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2

Bojadzic

Garnica

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and ACE2, which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable / less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound-library that is focused on the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel drug-like compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC50s of 0.2-3.0 μM); whereas, control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs identified here bind SARS-CoV-2-S and not ACE2. Selected promising compounds inhibited the entry of a SARS-CoV-2-S expressing pseudovirus into ACE2-expressing cells in concentration-dependent manner with low micromolar IC50s (6-30 μM). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for coronavirus attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases caused by coronaviruses in general and COVID-19 in particular.

show abstract

“… 24 Antibody-like monobodies designed to bound to the SARS-CoV-2 S protein also did not bind that of SARS-CoV. 25 As a further complicating factor, RNA viruses accumulate mutations over time, which yields antibody resistance and requires the use of antibody cocktails to avoid mutational escape. 26 Not surprisingly, there is now evidence of the emergence of SARS-CoV-2 mutants for which antibodies against the original strain have no or diminished activity.…”

mentioning

confidence: 99%

Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein–Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2

et al. 2021

View full text Add to dashboard Cite

Inhibitors of the protein–protein interaction (PPI) between the SARS-CoV-2 spike protein and human ACE2 (hACE2), which acts as a ligand–receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than that with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable/less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound library focused around the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel druglike compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC 50 ’s of 0.2–3.0 μM), whereas control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs of interest identified here bind SARS-CoV-2-S and not hACE2. While dyes seemed to be promiscuous inhibitors, DRI-C23041 showed some selectivity and inhibited the entry of two different SARS-CoV-2-S expressing pseudoviruses into hACE2-expressing cells in a concentration-dependent manner with low micromolar IC 50 ’s (6–7 μM). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for SARS-CoV-2 attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases caused by coronaviruses in general and COVID-19 in particular.

show abstract

Antibody-like proteins that capture and neutralize SARS-CoV-2

Cited by 50 publications

References 52 publications

Advances in emergent biological recognition elements and bioelectronics for diagnosing COVID-19

Advances in emergent biological recognition elements and bioelectronics for diagnosing COVID-19

Small-MoleculeIn VitroInhibitors of the Coronavirus Spike – ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2

Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein–Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2

Contact Info

Product

Resources

About