Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant

Schubert, Maren; Bertoglio, Federico; Steinke, Stephan; Heine, Philip Alexander; Ynga-Durand, Mario Alberto; Zuo, Fanglei; Du, Likun; Korn, Janin; Milošević, Marko; Wenzel, Esther Veronika; Maaß, Henrike; Krstanović, Fran; Polten, Saskia; Pribanic-Matesic, Marina; Brizić, Ilija; Piralla, Antonio; Baldanti, Fausto; Hammarström, Lennart; Dübel, Stefan; Šustić, Alan; Marcotte, Harold; Strengert, Monika; Protić, Alen; Hammarström, Qiang Pan; Čičin‐Šain, Luka; Hust, Michael

doi:10.1101/2021.12.10.21267523

Cited by 21 publications

(32 citation statements)

References 37 publications

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“…In the case of B. in-vitro tests show a 2.5 fold decrease in neutralization for B.1.617.2 using post-vaccinated sera (after 2 doses) (86). Initial reports also state a reduced neutralizing potency for the vaccine against B.1.1.529 (87). In the case of CanSinoBio (Convidecia), as per the report released by Pakistan authorities, initially, the vaccine demonstrated 65.7% efficacy in preventing symptomatic cases and a 90.98% success rate in stopping severe disease in an interim analysis of global trials.…”

Section: Mrna Vaccinesmentioning

confidence: 99%

“…Further, in-vitro tests show a 2.5 fold decrease in neutralization for B.1.617.2 using post-vaccinated sera (after 2 doses) ( 86 ). Initial reports also state a reduced neutralizing potency for the vaccine against B.1.1.529 ( 87 ).…”

Section: Impact On Vaccinesmentioning

confidence: 99%

“…Jongeneelen et al ( 93 ) report a 3.6-fold, 3.4-fold and 1.6-fold decrease in post-vaccine sera neutralization against B.1.351, P.1 and B.1.617.2, respectively. However, the vaccine showed a significant reduction in binding toward B1.1.529 RBD ( 87 ).…”

Section: Impact On Vaccinesmentioning

confidence: 99%

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SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

Thakur¹,

Sasi²,

et al. 2022

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With the high rate of COVID-19 infections worldwide, the emergence of SARS-CoV-2 variants was inevitable. Several mutations have been identified in the SARS-CoV-2 genome, with the spike protein as one of the mutational hot spots. Specific amino acid substitutions such as D614G and N501Y were found to alter the transmissibility and virulence of the virus. The WHO has classified the variants identified with fitness-enhancing mutations as variants of concern (VOC), variants of interest (VOI) or variants under monitoring (VUM). The VOCs pose an imminent threat as they exhibit higher transmissibility, disease severity and ability to evade vaccine-induced and natural immunity. Here we review the mutational landscape on the SARS-CoV-2 structural and non-structural proteins and their impact on diagnostics, therapeutics and vaccines. We also look at the effectiveness of approved vaccines, antibody therapy and convalescent plasma on the currently prevalent VOCs, which are B.1.17, B.1.351, P.1, B.1.617.2 and B.1.1.529. We further discuss the possible factors influencing mutation rates and future directions.

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Section: Mrna Vaccinesmentioning

confidence: 99%

Section: Impact On Vaccinesmentioning

confidence: 99%

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SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

Thakur¹,

Sasi²,

et al. 2022

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“…Omicron, the last variant of SARS-CoV-2 and now the dominant strain on the world, was found to bind to ACE2 receptors twice as strongly compared to previous variants (85). This increase in binding strength caused the virus to spread more quickly and spread the epidemic again.…”

Section: Omicron Variant and Multi-receptor Mechanismmentioning

confidence: 97%

Crosstalk among COVID-19, STRA6, Retinol, and G protein-coupled receptor may explain the novel hypothesis of Retinol depletion and retinoid signaling disorder of COVID-19 pathogenesis

Elkazzaz¹

2022

Preprint

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More than two years have passed since the pandemic and despite all the efforts of researchers, the pathogenesis of COVID-19 has not yet been resolved. Multisystem involvement, neuroendocrine involvement, and pathophysiological changes caused by SARS-CoV-2 in peripheral organs have been shown in many studies. However, the molecular mechanism of these pathophysiological changes caused by COVID-19 has not been elucidated. The frequent mutations of SARS-CoV-2 and the change in the interaction of the virus with host cells have further complicated the pathogenetic mechanism in COVID-19. Unfortunately, the mechanism determined at the beginning of the pandemic and based on the single receptor tropism of ACE2 was insufficient to explain the pathogenesis of COVID-19. It is known that SARS-CoV-2 causes retinoid signaling defects and chemosensory receptor disorders and exerts its pathogenic effects through these mechanisms. Multisystem involvement and different clinical presentations in COVID-19 suggest that virus-host interaction develops through multiple receptors and signaling pathways. The previous mechanism described via ACE2, based on single-receptor tropism, was insufficient to elucidate the pathogenesis of COVID-19 due to the absence of ACE2 receptors in most of the affected organs. In addition, there is no satisfactory explanation for the mechanism by which ACE2-free organs are affected in COVID-19. In this regard, we think that ACE2 is not a true binding receptor for the SARS-CoV-2 spike protein. With our recent molecular docking studies, STRA6 and its GPCRs were identified as new binding receptors of the SARS-CoV-2 spike protein. These studies have brought a multi-receptor mechanism to the pathogenesis of COVID-19. The multi-receptor mechanism clearly illuminates the complex pathogenesis of retinoid signaling disorder, systemic organ involvement, neuroendocrine involvement, loss of smell and taste, and many other peripheral symptoms and signs, which are considered an enigma in the pathogenesis of COVID-19. Therefore, we suggest retinoid signaling defect as the main pathogenetic disorder in COVID-19 and STRA6 and GPCRs as the main binding receptors of SARS-CoV-2 spike protein. This new mechanism also clarifies the changing symptoms and findings in COVID-19 with each new variant. Moreover, these studies have explained the novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder and have revealed new drug targets for the treatment and prophylaxis of COVID-19.

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“…As of yet, binding strength differences of SARS-CoV-2 VOCs' spike proteins to hACE2 are estimated controversially, depending on molecular modelling and simulation approaches [19][20][21][22][23][24]. Experimental data on binding strengths of SARS-CoV-2 Omicron's spike protein to hACE2 which so far have become available provide evidence that Omicron's RBD interaction with hACE2 is weaker than that of Delta's RBD [25][26][27], with one exception which states that binding strength of Delta's or Omicron's RBD to hACE2 was in similar ranges [28].…”

Section: Variant Of Concern and Human Bindingmentioning

confidence: 99%

From Free Binding Energy Calculations of SARS-CoV-2—Receptor Interactions to Cellular Immune Responses

2022

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Our study focuses on free energy calculations of SARS-CoV-2 spike protein receptor binding motives (RBMs) from wild type and variants of concern (VOCs), with emphasis on SARS-CoV-2 Omicron. Our computational analysis underlines the occurrence of positive selection processes that specify Omicron host adaption and bring changes on the molecular level into context with clinically relevant observations. Our free energy calculation studies regarding the interaction of Omicron’s RBM with human angiotensin converting enzyme 2 (hACE2) indicate weaker binding to the receptor than Alpha’s or Delta’s RBMs. Upon weaker binding, fewer viruses are predicted to be generated in time per infected cell, resulting in a delayed induction of danger signals as a trade-off. Along with delayed immunogenicity and pathogenicity, more viruses may be produced in the upper respiratory tract, explaining enhanced transmissibility. Since in interdependence on the human leukocyte antigen type (HLA type), more SARS-CoV-2 Omicron viruses are assumed to be required to initiate inflammatory immune responses, and because of pre-existing partial immunity through previous infections and/or vaccinations, which mostly guard the lower respiratory tract, overall disease severity is expected to be reduced.

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Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant

Cited by 21 publications

References 37 publications

SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

Crosstalk among COVID-19, STRA6, Retinol, and G protein-coupled receptor may explain the novel hypothesis of Retinol depletion and retinoid signaling disorder of COVID-19 pathogenesis

From Free Binding Energy Calculations of SARS-CoV-2—Receptor Interactions to Cellular Immune Responses

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