Increased immune escape of the new SARS-CoV-2 variant of concern Omicron

Hu, Jie; Peng, Pai; Cao, Xiaoxia; Wu, Kang; Chen, Juan; Wang, Kai; Tang, Ni; Huang, Ailong

doi:10.1038/s41423-021-00836-z

Cited by 205 publications

(181 citation statements)

References 12 publications

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“…A practical need was to map possible synergistic effects among the mutations of the VOCs and VOIs (J. Hu et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

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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“…A practical need was to map possible synergistic effects among the mutations of the VOCs and VOIs (J. Hu et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

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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“…Similarly, hamsters infected with wild type SARS-CoV-2, Alpha, Beta, or Delta strains showed a weight loss upto 10–17% by day 6 of infection, while hamsters infected with Omicron did not result in detectable weight loss despite higher challenge doses ( McMahan et al, 2022 ). With pseudotyped Omicron particles bearing all the S mutation with HIV virus backbone, a lower entry efficacy and less proteases cleavage have been observed in Omicron, suggestive of low replicative efficacy in HEK293T cells or ACE2 receptor expressing A549 cells ( Hu et al, 2022 ). While using the SARS-CoV-2 virus-like particles (VLPs) harbouring all the mutations present in the four structural genes of Omicron revealed an increase in infectivity ( Syed et al, 2022 ).…”

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

confidence: 99%

“…While using the SARS-CoV-2 virus-like particles (VLPs) harbouring all the mutations present in the four structural genes of Omicron revealed an increase in infectivity ( Syed et al, 2022 ). The difference in results between the pseudotyped Omicron particles ( Hu et al, 2022 ) that exhibit a lower entry efficacy and in SARS-CoV-2 like VLPs having Omicron like mutations that exhibited increased infectivity, possibly owing to the types of mutations incorporated in the said viruses and the cell line used for assay. E484K mutation is present in Beta and Gamma variants ( Kannan et al, 2022 ), while it is mutated to E484A in Omicron.…”

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

248

196

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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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“…Since the first report of a new SARS-CoV-2 variant of concern (VOC), Omicron (Pango lineage B.1.1.529), on November 19, 2021 1 , this VOC has rapidly disseminated globally and now dominates in many countries. Omicron carries more than 30 mutations and deletions in the spike gene compared to the original Wuhan strain and is associated with increased transmissibility 2 and immune escape 3,4 . Studies indicate that the Omicron variant results in less severe disease outcomes than Delta 5 .…”

Section: Introductionmentioning

confidence: 99%

Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

Stegger

Edslev

Sieber

et al. 2022

Preprint

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The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection. To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death. In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.

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Increased immune escape of the new SARS-CoV-2 variant of concern Omicron

Cited by 205 publications

References 12 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

Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

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