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Omicron: The New Panic Button

The Omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported as a variant of concern (VOC) by the World Health Organization (WHO) on November 26, 2021. The emergence of the Omicron variant has been attributed to three distinct processes: silent evolution in a population with limited sequencing; long-term evolution in one or a small number of people with chronic infection; or evolution in other animals, especially rodents. The Omicron variant has evolved into five distinct lineages known as BA.1, BA.2, BA.3, BA.4, and BA.5. It has been detected in more than 40 countries, including South Africa, Ghana, France, Nigeria, Botswana, Japan, South Korea, Russia, Nepal, India, Sri Lanka, Thailand, Malaysia, the Maldives, Singapore, Hong Kong, Israel, Canada, the United States, Mexico, Brazil, and Oceania.

BA.1 was previously the most widely distributed strain worldwide. BA.3 has only been reported to be transmissible in a few hundred cases at most. The Omicron variants have caused widespread concern and anxiety due to their infectious and vaccine-escape changes. Currently, up to 60 mutations have been discovered in the BA.1 lineage, with up to 38 found in the spike (S) protein, one in the envelope (E) protein, two in the membrane (M) protein, and six in the nucleocapsid (N) protein. The BA.2 lineage contains 57 mutations, 31 of which are in the S protein, whose N-terminus differs greatly from that of the BA.1 lineage. The S protein's receptor-binding domain (RBD) binds to the host angiotensin-converting enzyme 2 (ACE2) receptor and has the ability to boost infectiousness and facilitate escape from vaccine-induced neutralising antibodies. Therefore, the RBD of S protein mutations has sparked a lot of research interest. BA.1 and BA.2 share twelve mutations in the RBD, including G339D, S373P, S375F, K417N, N440K, S477N, T478K, E484A, Q493R, Q498R, N501Y, and Y505H. Only BA.1 had S371L, G446S, and G496S, while BA.1.1 was the only member of this group with R346K. BA.2 and BA.3 share T376A and D405N, as well as two distinct RBD mutations, S371F. Some of these changes, which are known to improve transmissibility, increase viral binding affinity, and cause antibody escape, have previously been discovered. For instance, it has been proposed that mutations in the residues K417, E484, and N501, which have previously been identified in Beta (B.1.351) and Gamma (P.1) variations, may mediate escape from vaccine-induced neutralisation. Most of the remaining Omicron mutations have unknown effects, so it is still uncertain how the virus behaves and how susceptible it is to inborn and vaccine-mediated protection. Additionally, this novel variation can re-infect those who have already contracted other SARS-CoV-2 forms. According to a recent study, people who are recuperating from illnesses caused by previously common variants are likely to contract the Omicron variant. This study demonstrates that Omicron mutations circumvent the immunity brought up by the earlier infection.

It has been proposed, for example, that mutations in the K417, E484, and N501 residues, which have previously been identified in Beta (B.1.351) and Gamma (P.1) variations, may mediate escape from vaccine-induced neutralisation. Most of the remaining Omicron mutations have unknown effects, so it is still uncertain how the virus behaves and how susceptible it is to inborn and vaccine-mediated protection. Furthermore, this novel variant has the potential to re-infect people who have previously been infected with other SARS-CoV-2 strains. A recent study found that people recovering from illnesses caused by previously common variants are more likely to contract the Omicron variant. This study shows that Omicron mutations bypass the immunity induced by the previous infection.

The Omicron variant is predicted to be 10 times more contagious than the original SARS-CoV-2 and about twice as infectious as the Delta variant because of the mutations in the RBD, including N440K, T478K, and N501Y. Further, it has a very high potential to interrupt the binding of almost 132 antibodies with the S protein, and that is due to its RBD mutations K417N, E484A, and Y505H, indicating its stronger vaccine breakthrough capability than the Delta variant. As a complete scenario, mutations effectively enhance the BFE changes, resulting in a stronger binding affinity of the ACE2-RBD complex and making the variant more infectious. All of this proves that Omicron appears to have followed the infectivity-strengthening pathway of natural selection. Taken together, spike mutations of Omicron have also been identified in the other VOC variants, such as D614G, N501Y, K417N, P681H, and the residue substitution of E484. These mutations have been indicated in higher binding affinity with ACE2, enhanced transmissibility and pathogenicity, and reduced ability of neutralization by monoclonal antibodies and immune evasion. Omicron variant spike protein has more hydrophobic amino acids (AA)- Phenylalanine and Isoleucine in comparison to the delta because of its positioning inside the protein core. There is alternation amino acid composition containing Arginine (Arg), Lysine, (Lys), Aspartic acid (Asp), and Glutamic acid (Glu) indicating that omicron has more charged residues and are exposed to much greater degree. In comparison to the delta version, the omicron’s AA composition in terms of polar AA like Asparagine (N) and Glutamine (Q) is low, while in RBD the non-polar AA like Leucine (L), Phenylalanine (F), and Proline (P) are higher. These residues are present on the inner side of the protein core and are thus inaccessible to the solvent. Omicron variant has higher α-helix structure (23.46%) in comparison to delta variant (22.03%), which accounts for its more stability

The Omicron variant's capability for immune evasion is a serious concern. It is highly transmissible due to its ability to bypass immune defences built up from vaccination or prior infection with another variant. According to UK data, BA.2 and BA.1 are both capable of evading the immune system. In addition, despite the modest number of cases that have been reported, a recent investigation demonstrated that BA.2 can re-infect BA.1 convalescent patients. The RBD region and N-terminal domain (NTD) of the Omicron variant have a number of alterations that are the primary targets of neutralization. Unprecedented complexities in mutation patterns can alter antigenicity and render immunity ineffective. The ability of the Omicron variant to evade immune detection is a major concern. It is highly contagious due to its ability to evade immune defences developed through vaccination or prior infection with another variant. As per the UK data, variants BA.1 and BA.2 are both capable of evading the immune system. Furthermore, despite the small number of reported cases, a recent study found that BA.2 can re-infect BA.1 convalescent patients. The Omicron variant's RBD region and N-terminal domain (NTD) have a number of alterations that are the primary targets of neutralisation. Antigenicity can be altered and immunity rendered ineffective by unprecedented complexities in mutation patterns. Cryo-electron microscopy is used to reveal the structure of Omicron's immune evasion mechanism (cryo-EM). While a single-up conformation and an all-down conformation were shown in earlier variations, Omicron S-trimer only created one conformational state with one "up" RBD and two "down" RBDs. Mutations that disrupted antibody recognition resulted in steric conflicts, altered interactions at antibody-binding surfaces, and local spike structure changes.

Vaccination has been proven to be the most effective means for prevention and control of COVID-19. There are four categories of vaccines, i.e., virus vaccines, viral-vector vaccines, DNA/RNA vaccines, and protein-based vaccines. The current COVID-19 vaccines used mainly target the S protein of the virus. As per the researchers, the 32 amino acid alterations in the Omicron, which include three small deletions and one small insertion in the S protein, suggest that the Omicron may be induced by vaccination. All these mutations may increase the variant's capability to evade current vaccines. The mutation in the Omicron RBD can effectively alter the binding pattern of the known antibodies. As per the current studies, the Omicron mutations favour the escape of current vaccines. The impact of Omicron on ACE2 is significantly weak, which indicates that SARS-CoV-2 has already optimised its binding with ACE2, and there is a relatively limited scope for the virus to improve its infectivity to the host. Studies also suggest that variants may become more destructive to vaccines in the coming years.

The COVID variant omicron has rapidly grown into a number of subvariants since it first appeared in late 2021. An increase in COVID infections across China is being attributed to the subvariant BF.7, which has recently been identified as the major variant spreading in Beijing. The omicron variant BA.7 has a sublineage of the omicron variant BA.5, abbreviated as BA. As per the reports from China, BF.7 has the strongest capacity for infection amongst the other Omicron subvariants. It spreads faster than other variants, has a shorter incubation period, and is more likely to infect people who have previously contracted COVID, received a COVID vaccination, or both. R0, or the fundamental reproduction number, for BF.7 is thought to be between 10 and 18.6. The high rate of BF.7 transmission, combined with the risk of masked spread caused by the large number of asymptomatic carriers, is thought to be making it extremely difficult to control the epidemic in China. Over time, new omicron subvariants have emerged that are better able to avoid vaccination or infection-induced immunity. BF.7 is no exception. The R346T mutation exists in the SARS-CoV-2 spike protein in BF.7 (a protein on the surface of the virus that allows it to attach to and infect living cells). This mutation, which is also found in the "parent" form of BF.7, BA.5, has been linked to the virus's ability to avoid neutralising antibodies produced by vaccination or prior infection. A recent study looked at BF.7 neutralisation in sera (a component of blood that should contain antibodies) from triple-vaccinated healthcare workers as well as patients infected during the pandemic's omicron BA.1 and BA.5 waves. The R346T mutation contributed to BF.7's resistance to neutralisation.

There is an urgent need for in-depth research and understanding of Omicron as it poses a significant risk to public health and may jeopardize efforts to restrict the COVID-19 pandemic.

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