Charge Matters: Mutations in Omicron Variant Favor Binding to Cells

Nie, Chuanxiong; Sahoo, Anindita; Herrmann, Andreas; Ballauff, Matthias; Netz, Roland R.; Haag, Rainer

doi:10.1002/cbic.202100681

Cited by 66 publications

(66 citation statements)

References 34 publications

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“…The RBD Omicron is clearly the system with the highest affinity for ACE2 wt . This result for Omicron is qualitatively in agreement with several other theoretical calculations that are appearing in the literature (Ford et al, 2021; Han et al, 2022; Hanai, 2022; Lan et al, 2022; Lupala et al, 2022; Nie et al, 2022, 2022; Ortega et al, 2021). For example, Ortega and colleagues reported the values of − 109.8(3.5) and − 163.8(4.1) for the Haddock score function for the wt and Omicron, respectively (Ortega et al, 2021).…”

Section: Resultssupporting

confidence: 92%

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

Giron

Laaksonen

Silva

2022

Preprint

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SARS-CoV-2 has caused immeasurable damage worldwide and available treatments with high efficacy are still scarce. With the continuous emergence of new variants of the virus, such as Omicron, Alpha, Beta, Gamma, and Delta - the so-called variants of concern, the available therapeutic and prevention strategies had to return to the experimental trial to verify their effectiveness against them. This work aims to expand the knowledge about the SARS-CoV-2 receptor-binding domain (RBD) interactions with cell receptors and monoclonal antibodies (mAbs). Special attention is given to the Omicron variant and its comparison with the others, including its sublineage BA.2 and two new ones (B.1.640.1 and B.1.640.2/IHU) recently found in France. By using constant-pH Monte Carlo simulations, the free energy of interactions between the SARS-CoV-2 receptor-binding domain (RBD) from different variants and several partners (Angiotensin-Converting Enzyme-2 (ACE2) polymorphisms and several mAbs) were calculated. It was evaluated both the impact of mutations for the RBD-ACE2 and how strongly each of mAb can bind to the virus RBD, which can indicate their therapeutic potential for neutralization. RBD-ACE2-binding affinities were higher for two ACE2 polymorphisms typically found in Europeans (rs142984500 and rs4646116), indicating that these types of polymorphisms may be related to genetic susceptibility to COVID-19. The antibody landscape was computationally investigated with the largest set of mAbs so far in the literature. From the 33 studied binders, groups of mAbs were identified with weak (e.g. S110 and Ab3b4), medium (e.g. CR3022), and strong binding affinities (e.g. P01prime, S2K146 and S230). All the mAbs with strong binding capacity could also bind to the RBD from SARS-CoV-1, SARS-CoV-2 wt, and all studied variants. These mAbs and especially their combination are amenable to experimentation and clinical trials because of their high binding affinities and neutralization potential for current known virus mutations and a universal coronavirus.

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Section: Resultssupporting

confidence: 92%

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

Giron

Laaksonen

Silva

2022

Preprint

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“…Omicron N terminal domain has also poor affinity for lipid rafts that made Omicron less fusogenic and low pathogenic ( Fantini et al, 2022 ). In spike protein, Omicron is having 5 additional positively charged amino acids in comparison to wild type virus that is enhancing the binding of Omicron virus with the cellular targeted drug development ( Nie et al, 2022 ).…”

Section: Is the Severity For Omicron Is Less Than Its Other Voc Cousins?mentioning

confidence: 99%

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

Khandia

Singhal

Alqahtani

et al. 2022

Environmental Research

206

152

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Since the appearance in the late of December 2019, SARS-CoV-2 is rapidly evolving and mutating continuously, giving rise to various variants with variable degrees of infectivity and lethality. The virus that initially appeared in China later mutated several times, wreaking havoc and claiming many lives worldwide amid the ongoing COVID-19 pandemic. After Alpha, Beta, Gamma, and Delta variants, the most recently emerged variant of concern (VOC) is the Omicron (B.1.1.529) that has evolved due to the accumulation of high numbers of mutations especially in the spike protein, raising concerns for its ability to evade from pre-existing immunity acquired through vaccination or natural infection as well as overpowering antibodies-based therapies. Several theories are on the surface to explain how the Omicron has gathered such a high number of mutations within less time. Few of them are higher mutation rates within a subgroup of population and then its introduction to a larger population, long term persistence and evolution of the virus in immune-compromised patients, and epizootic infection in animals from humans, where under different immune pressures the virus mutated and then got reintroduced to humans. Multifaceted approach including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, efficacy testing of vaccines and immunotherapies against newly emerged variants, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going SARS-CoV-2 pandemic successfully.

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“…The article written by Nie et al. pointed out that the higher infection potential of the Omicron variant of SARS‐CoV‐2 can be attributed to multivalent charge‐charge interactions with anionic receptors [1] . This view has furthered our understanding on the etiology of COVID‐19.…”

Section: Figurementioning

confidence: 99%

“…The proteins of SARS‐CoV‐2 and SARS are generally overrepresented in valine plus glycine [3] . The spike protein of the Omicron variant harbors several amino acid substitutions by lysine [1] . These features are biochemically intriguing due to the chemical attributes of amino acids which render this variant less lethal.…”

Section: Figurementioning

confidence: 99%

“…The antagonism between insoluble salts and acids or strong anions is widespread in cells (Figure 1). [4,6] The basic amino acid arginine can bind calcium [7] enhancing the formation of stressful calcium oxalate, which explains the lethality associated with several arginine replacements in Delta variant of SARS‐CoV‐2 [1,2] . There are a few scenarios on the origin of the Omicron variant including a potential zoonotic origin.…”

Section: Figurementioning

confidence: 99%

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Why Omicron Variant of SARS‐CoV‐2 is Less Fatal?

et al. 2022

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The article published by Nie et al. addressed one of the two key questions regarding the Omicron variant of SARS-CoV-2, while the underpinning for the less deadly nature of the variant remains unexplained. The proteins of the Omicron variant have numerous mutations, notably several substitutions of other amino acids by lysine residues. Glycine and valine attract calcium and enhance the formation of stressful, insoluble, and stiff calcium oxalate. Lysine residues in proteins build up [a

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Charge Matters: Mutations in Omicron Variant Favor Binding to Cells

Cited by 66 publications

References 34 publications

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

Why Omicron Variant of SARS‐CoV‐2 is Less Fatal?

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