Impact of the temperature on the interactions between common variants of the SARS-CoV-2 receptor binding domain and the human ACE2

Forest-Nault, Catherine; Koyuturk, Izel; Gaudreault, Jimmy; Pelletier, Alex; L’Abbé, Denis; Cass, Brian; Bisson, Louis; Burlacu, Alina; Delafosse, Laurence; Stuible, Matthew; Henry, Olivier; Crescenzo, Grégory De; Durocher, Yves

doi:10.1038/s41598-022-15215-5

Cited by 14 publications

(10 citation statements)

References 57 publications

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“…The L452R mutation is still debated in several studies , since it does not play a crucial role in the interaction with ACE2. However, a paper by Forest-Nault and co-workers suggests that the L452R mutation abrogates a hydrophobic patch formed by residues L452, L492, and F490. The loss of this patch could impact the stability of the RBD and possibly its complexation with ACE2, where faster association and dissociation of the RBD have been observed …”

Section: Resultsmentioning

confidence: 99%

“…The loss of this patch could impact the stability of the RBD and possibly its complexation with ACE2, where faster association and dissociation of the RBD have been observed. 157 New hot spots have also been detected on the RBM surface due to the introduction of several mutations in each variant. The N501Y mutation is common to the Alpha, Beta, Gamma, and Omicron variants, indicating this mutation confers strong advantages to the SARS-CoV-2 virus.…”

Section: Binding Free Energy Analysismentioning

confidence: 99%

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Comparative Study of the Mutations Observed in the SARS-CoV-2 RBD Variants of Concern and Their Impact on the Interaction with the ACE2 Protein

Ghoula,

Deyawe Kongmeneck,

Eid

et al. 2023

J. Phys. Chem. B

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SARS-CoV-2 strains have made an appearance across the globe, causing over 757 million cases and over 6.85 million deaths at the time of writing. The emergence of these variants shows the amplitude of genetic variation to which the wild-type strains have been subjected. The rise of the different SARS-CoV-2 variants resulting from such genetic modification has significantly affected COVD-19’s major impact on proliferation, virulence, and clinics. With the emergence of the variants of concern, the spike protein has been identified as a possible therapeutic target due to its critical role in binding to human cells and pathogenesis. These mutations could be linked to functional heterogeneity and use a different infection strategy. For example, the Omicron variant’s multiple mutations should be carefully examined, as they represent one of the most widely spread strains and hint to us that there may be more genetic changes in the virus. As a result, we applied a common protocol where we reconstructed SARS-CoV-2 variants of concern and performed molecular dynamics simulations to study the stability of the ACE2–RBD complex in each variant. We also carried out free energy calculations to compare the binding and biophysical properties of the different SARS-CoV-2 variants when they interact with ACE2. Therefore, we were able to obtain consistent results and uncover new crucial residues that were essential for preserving a balance between maintaining a high affinity for ACE2 and the capacity to evade RBD-targeted antibodies. Our detailed structural analysis showed that SARS-CoV-2 variants of concern show a higher affinity for ACE2 compared to the Wuhan strain. Additionally, residues K417N and E484K/A might play a crucial role in antibody evasion, whereas Q498R and N501Y are specifically mutated to strengthen RBD affinity to ACE2 and, thereby, increase the viral effect of the COVID-19 virus.

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Section: Resultsmentioning

confidence: 99%

Section: Binding Free Energy Analysismentioning

confidence: 99%

Comparative Study of the Mutations Observed in the SARS-CoV-2 RBD Variants of Concern and Their Impact on the Interaction with the ACE2 Protein

Ghoula,

Deyawe Kongmeneck,

Eid

et al. 2023

J. Phys. Chem. B

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“…Recombinant, “tagless” Spike proteins were produced as previously described 66 . Recombinant RBD protein was produced as previously described 67,68 . Spike variant BA.2 (omicron) was obtained through BEI Resources, NIAID, NIH: Spike Glycoprotein (Stabilized) from SARS-Related Coronavirus 2, BA.2 Lineage (Omicron Variant) with C-Terminal Histidine and Avi Tags, Recombinant from HEK293 Cells, NR-56517.…”

Section: Methodsmentioning

confidence: 99%

“…Recombinant, "tagless" Spike proteins were produced as previously described 66 . Recombinant RBD protein was produced as previously described 67,68 . Spike variant BA.2 (omicron) was obtained through BEI Resources, NIAID, NIH:…”

Section: Generation Of Ad(spike) Vectormentioning

confidence: 99%

BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine

Perera

Domenech

Babuadze

et al. 2023

Preprint

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Despite medical interventions and several approved vaccines, the COVID-19 pandemic is continuing into its third year. Recent publications have explored single-dose intranasal (i.n.) adenovirus-based vaccines as an effective strategy for curbing SARS-CoV-2 in naive animal models. However, the effects of prior immunizations and infections have yet to be considered within these models. Here, we investigate the immunomodulatory effects of Mycobacterium bovis BCG pre-immunization on a subsequent S-protein expressing i.n. Ad vaccination, termed Ad(Spike). We found that Ad(Spike) alone conferred long-term protection from severe SARS-CoV-2 pathology within a mouse model, yet it was unable to limit initial infection 6 months post-vaccination. While i.n. Ad(Spike) retains some protective effect after 6 months, a single administration of BCG-Danish prior to Ad(Spike) vaccination potentiates its ability to control viral replication of the B.1.351 SARS-CoV-2 variant within the respiratory tract. Though BCG-Danish had no effect on the ability of Ad(Spike) to generate and maintain humoral immunity, it promoted the generation of cytotoxic and Th1 responses over suppressive FoxP3+ TREG cells in the lungs of infected mice. These data demonstrate a novel vaccination strategy that may prove useful in limiting future viral pandemics by potentiating the long-term efficacy of next generation mucosal vaccines within the context of the safe and widely distributed BCG vaccine.

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“…Among coiled-coils, the bioinspired Ecoil (EVSALEK) 5 and Kcoil (KVSALKE) 5 peptide pair has been successfully used for the oriented capture of bioactive proteins in surface plasmon resonance (SPR) biosensing, − enzyme-linked immunosorbent assays (ELISA), recombinant protein purification, as well as capture of proteins on cell culture compatible surfaces and hydrogels . More specifically, fusion proteins have been genetically modified to express an Ecoil tag, while the complementary Kcoil partner was covalently grafted onto a surface.…”

Section: Introductionmentioning

confidence: 99%

Grafting Strategies of Oxidation-Prone Coiled-Coil Peptides for Protein Capture in Bioassays: Impact of Orientation and the Oxidation State

Dégardin,

Gaudreault,

Oliverio

et al. 2023

ACS Omega

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Many biomedical and biosensing applications require functionalization of surfaces with proteins. To this end, the E/K coiled-coil peptide heterodimeric system has been shown to be advantageous. First, Kcoil peptides are covalently grafted onto a given surface. Ecoil-tagged proteins can then be non-covalently captured via a specific interaction with their Kcoil partners. Previously, oriented Kcoil grafting was achieved via thiol coupling, using a unique Kcoil with a terminal cysteine residue. However, cysteine-terminated Kcoil peptides are hard to produce, purify, and oxidize during storage. Indeed, they tend to homodimerize and form disulfide bonds via oxidation of their terminal thiol group, making it impossible to later graft them on thiol-reactive surfaces. Kcoil peptides also contain multiple free amine groups, available for covalent coupling through carbodiimide chemistry. Grafting Kcoil peptides on surfaces via amine coupling would thus guarantee their immobilization regardless of their terminal cysteine's oxidation state, at the expense of the control over their orientation. In this work, we compare Kcoil grafting strategies for the subsequent capture of Ecoil-tagged proteins, for applications such as surface plasmon resonance (SPR) biosensing and cell culture onto protein-decorated substrates. We compare the "classic" thiol coupling of cysteine-terminated Kcoil peptides to the amine coupling of (i) monomeric Kcoil and (ii) dimeric Kcoil−Kcoil linked by a disulfide bond. We have observed that SPR biosensing performances relying on captured Ecoil-tagged proteins were similar for amine-coupled dimeric Kcoil−Kcoil and thiol-coupled Kcoil peptides, at the expense of higher Ecoil-tagged protein consumption. For cell culture applications, Ecoil-tagged growth factors captured on amine-coupled monomeric Kcoil signaled through cell receptors similarly to those captured on thiol-coupled Kcoil peptides. Altogether, while oriented thiol coupling of cysteine-terminated Kcoil peptides remains the most reliable and versatile platform for Ecoil-tagged protein capture, amine coupling of Kcoil peptides, either monomeric or dimerized through a cysteine bond, can offer a good alternative when the challenges and costs associated with the production of monomeric cysteine-tagged Kcoil are too dissuasive for the application.

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Impact of the temperature on the interactions between common variants of the SARS-CoV-2 receptor binding domain and the human ACE2

Cited by 14 publications

References 57 publications

Comparative Study of the Mutations Observed in the SARS-CoV-2 RBD Variants of Concern and Their Impact on the Interaction with the ACE2 Protein

Comparative Study of the Mutations Observed in the SARS-CoV-2 RBD Variants of Concern and Their Impact on the Interaction with the ACE2 Protein

BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine

Grafting Strategies of Oxidation-Prone Coiled-Coil Peptides for Protein Capture in Bioassays: Impact of Orientation and the Oxidation State

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