Effect of RBD mutations in spike glycoprotein of SARS-CoV-2 on neutralizing IgG affinity
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Abstract
Background
Certain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subspecies (B.1.1.7, B.1.351, and B.1.1.248).
Methods
We investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F and N501Y on neutralizing antibodies in serum derived from COVID-19-positive patients.
Results
Our results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients.
Conclusions
Infection with SARS-CoV-2 subspecies that cause serious symptoms in humans may spread globally.
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SciScore for 10.1101/2021.01.28.21250577: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Data (PDB: 6XC2, 6XC4, 7JMP, 7JMO, 6XKQ, and 6XKP) (Supplementary Figure 4) on the three- dimensional structure of six neutralizing antibodies (CC12.1, CC12.3, COVA2-39, COVA2-04, CV07-250, and CV07-270) (Supplementary Figure 4) that bind to the spike glycoprotein of SARS- CoV-2 was used in these studies [6]. CV07-250suggested: NoneCV07-270suggested: NoneWe investigated the binding of the spike glycoprotein Y453F mutant of SARS-CoV-2 to human … SciScore for 10.1101/2021.01.28.21250577: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Data (PDB: 6XC2, 6XC4, 7JMP, 7JMO, 6XKQ, and 6XKP) (Supplementary Figure 4) on the three- dimensional structure of six neutralizing antibodies (CC12.1, CC12.3, COVA2-39, COVA2-04, CV07-250, and CV07-270) (Supplementary Figure 4) that bind to the spike glycoprotein of SARS- CoV-2 was used in these studies [6]. CV07-250suggested: NoneCV07-270suggested: NoneWe investigated the binding of the spike glycoprotein Y453F mutant of SARS-CoV-2 to human angiotensin-converting enzyme 2 (ACE2) and determined the affinity of the spike glycoprotein Y453F mutant of SARS-CoV-2 to six neutralizing monoclonal antibodies using the MOE program (three-dimensional protein structure modeling, protein docking analysis: MOLSIS Inc., Tokyo, Japan) and Cn3D macromolecular structure viewer. ACE2suggested: NoneThe amount of the bound ACE2, which is proportional to ACE2 inhibition intensity, is then recognized by the Neutralizing Detection Complex containing anti-His antibody and measured through an ELISA-like reaction by reading the absorbance in a microplate spectrophotometer at a wavelength of 450 nm. anti-Hissuggested: NoneSerum from 10 normal (negative for COVID-19) patients and 20 COVID-19 patients with varying immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels. immunoglobulin G (IgGsuggested: NoneCOVID-19 status was confirmed with RT-PCR, antigen, and/or antibody serology tests. RT-PCR, antigen,suggested: NoneExperimental Models: Cell Lines Sentences Resources Adsorption of RBD or RBD Y453F recombinant protein to the solid phase surface of the ELISA plate: HeLa cells were then transfected with pcMV3-2019-nCov-RBD-Flag tag expression vector (2 μg), or the pcMV3-2019-nCov-RBD Y453F-FLag tag expression vector (2 μg) ( HeLasuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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