IPSIndian Journal of Pharmacology
Home  IPS  Feedback Subscribe Top cited articles Login 
Users Online : 1222 
Small font sizeDefault font sizeIncrease font size
Navigate Here
Resource Links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (686 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)

In This Article
 »  Abstract
 » Introduction
 » Conclusion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    PDF Downloaded39    
    Comments [Add]    
    Cited by others 2    

Recommend this journal


 Table of Contents    
Year : 2022  |  Volume : 54  |  Issue : 1  |  Page : 41-45

Update on omicron variant: What we know so far

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission14-Dec-2021
Date of Decision24-Jan-2022
Date of Acceptance25-Jan-2022
Date of Web Publication18-Mar-2022

Correspondence Address:
Dr. Bikash Medhi
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijp.ijp_955_21

Rights and Permissions

 » Abstract 

The new omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in South Africa in November 2021 has been declared as a Variant of Concern by the World Health Organization. This variant has been found to carry multifold mutations that have not been observed in any of the variants detected so far. The majority of these mutations are present in spike protein, contributing to its ability to escape the currently available neutralizing antibodies and vaccines, as well as increasing the chances of reinfection. This brief communication provides an insight into mutations detected in the omicron variant and their impact on currently available interventions against SARS-CoV-2 and the need for a booster dose. We also discuss the severity status of infection due to this variant. Additionally, we highlight the hypothesis supporting the association of high HIV prevalence and the appearance of the omicron variant of SARS-CoV-2 in immune-compromised individuals.

Keywords: COVID-19, HIV, mutations, omicron, severe acute respiratory syndrome coronavirus 2, variant

How to cite this article:
Choudhary G, Prajapat M, Kumaravel J, Prabha PK, Sarma P, Handa V, Kaur H, Patel AP, Medhi B. Update on omicron variant: What we know so far. Indian J Pharmacol 2022;54:41-5

How to cite this URL:
Choudhary G, Prajapat M, Kumaravel J, Prabha PK, Sarma P, Handa V, Kaur H, Patel AP, Medhi B. Update on omicron variant: What we know so far. Indian J Pharmacol [serial online] 2022 [cited 2023 Feb 1];54:41-5. Available from: https://www.ijp-online.com/text.asp?2022/54/1/41/339918

Gajendra Choudhary and Manisha Prajapat Indicates equal authorship

 » Introduction Top

Omicron (or B.1.1.529 variant) was first reported in Botswana, South Africa, in early November 2021 and eventually designated to be a variant of concern (VOC) by the World Health Organization on November 26, 2021.[1] The name B.1.1.529 is named as per the Pango system to denote that its lineage goes back to its ancestor.[2] A steep rise in SARS-CoV-2 cases was also observed in those regions of South Africa where the omicron variant emerged.[3] The identification of this most mutated nCoV-2 variant is triggering alarm in all worldwide.[4]

Even WHO has warned all the countries against the new omicron variant, owing to its higher rate of transmission and re-infection rate compared to the delta variant.[5] Omicron is fifth VOC, after alpha, beta, gamma, and delta variant.[4] After being first detected in South Africa, omicron variant has also been reported in countries such as Germany, The Netherlands, Hong Kong, Australia, Italy, Botswana, Israel, Belgium, and Britain.[6],[7]

As stated by few research groups, working on exploring the genome of different SARS-CoV-2 variants, the novel variant omicron has been found to exhibit a “very unusual constellation of mutations,” which raises many concerns as this might enable its spike protein to evade antibodies produced during either a vaccination or a previous coronavirus infection.[4] Notably, these mutations in new variant might also be associated with higher transmission, stronger affinity for binding to host cells, and antibody escape.[8]

The various mutations observed in the structure of spike protein suggest that presently available drugs targeting the attachment of SARS-CoV-2 virus to the host cell may not turn out to be the treatment of choice against infection due to omicron variant.[8]

In this brief communication, we aim at providing the description of mutations observed in omicron variant of SARS-CoV-2 and their impact on currently available therapeutic strategies. Furthermore, we briefly describe the clinical features that have been observed in case of COVID-19 infection due to omicron. We also highlight the hypothesis that has been proposed for the emergence of this new variant of SARS-CoV-2.

Mutations in omicron

Several mutations have been detected in SARS-CoV-2 variants worldwide.[2],[9] In case of omicron (Gene Bank Ref Seq: NC_045512.2), genomic sequencing revealed nearly 51 mutations, comprising insertions, deletions, missense mutations, substitutions, and other mutations [Table 1].[2],[10],[11] Omicron variant has substitution mutations for 44 amino acids, deletion for 6 amino acids, and insertion mutation at one amino acid position. Most of the mutations were found in spike protein (S), i.e., 1 insertion, 3 deletions, and 29 substitutions (namely, A76V, T95I, 142-144del, Q498R, E484A, G339D, G446S, G339D, N440K, S477N, Q493R, T478K, G496S, Y505H, T547K, H655Y, N501Y, D614G, N679K, S371 L, N764K, P681H, D796Y, N856K, N969K, Q954H, L981F, S373P, L212I, S375F, N969K, K417N, and ins214EPE).[11] Some new mutations were also seen in spike protein along with the previously known mutations.[2],[12] For instance, the insertion mutation in spike protein (ins214EPE) is a new mutation that was not found in any of the previous SARS-CoV-2 variant. The receptor-binding domain (RBD) region of spike protein contains a total of 15 mutations. According to Chen et al., delta variant had 5 mutations in spike region that contributed to its high infection rate and spread worldwide. However, omicron variant has mutations even more than the previous delta variant, raising a concern regarding its transmissibility.[13] Different proteins of omicron variant such as E protein (mutated at T9I), M protein (mutated at Q19E, A63T, and D3G), nucleocapsid protein (mutated at R203K, G204R, and P13L) and Non-Structural Proteins (NSPs) (mutated at P323L and T492I) have also been examined for the presence of mutations[13],[14] [Table 1]. Some of these mutations are known to be associated with altered receptor interaction, transmissibility, and immune escape.[15]
Table 1: Mutations found in the omicron variant

Click here to view

The spike protein (s1) aids in binding of the virus to the angiotensin-converting enzyme-2 (ACE2) receptor of the host cell and has a major role in viral infectivity.[13],[16],[17] Receptor recognition is critical for the viral genome to be released into the cytoplasm of the host cells, followed by viral replication, ultimately leading to infection.[18],[19],[20] Upon investigation, it was revealed that the binding free energy between spike RBD and host ACE2 receptor is directly proportional to virus infectivity. Based on this observation, aim to decrease the viral infection rate via monoclonal antibodies targeting the RBD of spike protein was the most exploited approach to deal with COVID-19 infection in case of previously known variants. However, mutations in RBD region of spike protein would ultimately affect the affinity and efficacy of currently available antibodies and vaccines as well as increase the chances of reinfection.[13] According to in silico study, the RBD region of omicron makes stronger interaction (electrostatic interaction and hydrogen bonding) with ACE2 host cell receptor.[21] [Figure 1] depicts the structure of omicron variant along with the associated mutations.
Figure 1: The key mutation in omicron variant. Note that the mutations have been marked in red

Click here to view

In early 2020, TopNetmAb model model predicted that the mutational residues 452 and 501 were located in the spike protein region. These two residues have a higher mutation rate in more infectious strains of SARS-CoV-2 virus, as confirmed in variants such as alpha (α), beta (β), gamma (γ), delta (ծ), theta (ø), lambda (λ), mu (μ), and presently omicron which have mutation at position L452R/Q and N501Y.

[Table 2] depicts the total number of mutations found in different SARS-CoV-2 variants.
Table 2: Total mutations in 5 variants of SARS-CoV-2

Click here to view

The TopNetmAb model study found that omicron is ten times more infectious compared to other strains of SARS-CoV-2. The spike RBD region of omicron has mutations at N440K, T478K, and N501Y residues, making omicron twofold more infectious compared to delta variant. Other mutations on spike RBD region of omicron such as K417N, E484A, and Y505H are able to prevent the binding of most antibodies (approximately 132) against RBD region of omicron.[13] The interactivity between RBD domain of omicron S protein and ACE2 host cell receptor has increased remarkably due to mutation at the site of K417N, Q493R, N501Y, and Y505H residues[22] [Figure 1]. Mutations in other proteins of such as in nucleocapsid protein at positions R203K and G204R further increase the viral RNA expression and viral load.[12] One of the monoclonal antibody cocktail developed by Eli Lilly has reduced efficacy against omicron due to mutations at K417N, E484A, and Q493R residue positions in RBD region of virus.[13] Other examples like Rockefeller University monoclonal antibody whose binding capacity has also been reduced due to mutation at position E484A in the RBD region.[13],[23] Furthermore, BNT162b2 antibody was found to neutralize two omicron variant isolates, namely HKU691 and HKU344-R346K, with an efficacy of 20% and 24%, respectively.[24] Therefore, a more efficacious vaccine would be required against it.[13]

Clinical features and severity of omicron infection

As per the CDC genomic surveillance, there are some new mutations of the COVID-19 being tracked to help public health officials to make better decisions. New variant of COVID-19, B.1.1.529 was first reported to the WHO. Following this WHO named this variant as Omicron and classified it as Variant of Concern (VOC).[25] Subvariants like BA.1 and BA.2 are documented as per the current evidence and research. Clinical features for these subvariants are not yet established fully. Clinical features of omicron are categorized in the [Table 3].[26]
Table 3: Clinical features of omicron

Click here to view


As per the recent WHO guidelines for COVID-19 updated on 24th Feb 2022, COVID-19 should be treated according to the disease severity. For patients does not require supplemental oxygen therapy, the panel is strongly against the use of corticosteroids like dexamethasone but if the patient already on dexamethasone for underlying condition can continue. As per the panel recommendations for the hospitalized patients who require supplemental oxygen, any one of the following can be used includes remdesivir, dexamethasone plus remdesivir, add on second immunomodulatory drug like tocilizumab or baricitinib can be used for rapidly increasing oxygen demand and severe systemic inflammation. Regarding the alternatives, IV sarilumab can be used instead of IV tocilizumab and tofacitinib can be used instead of baricitinib. Anticoagulant therapy can be considered according to the severity of the disease. [Table 4] As per WHO Living guidelines of COVID-19 (January 2022), there is conditional recommendation for the use of new monoclonal antibody sotrovimab in patients with non-severe COVID-19 disease at higher risk of hospitalization.[27],[28] Interleukin-6 (IL-6) inhibitor: Tocilizumab is considered on a case to case based prefer within 24 to 48 hours of progress of severe disease. It is considered in cases where no improvement is observed in the levels of significantly raised inflammatory markers.[29] The current treatment guidelines would be suitable against the omicron variant specifically drugs for symptomatic relief and steroids and IL6 antagonist.[30] Recently FDA sanctioned Emergency use authorization (EUA) to a combination of ritonavir and nirmatrelvir tablets (Paxlovid) for the treatment of COVID-19.[31]
Table 4: Anticoagulation therapy can be considered according to the severity

Click here to view

Management of Omicron variant

Symptomatic management is the only effective measures available for this variant. There is no approved drug available for this variant to up to date. According to preliminary results, Omicron has a 13fold higher viral infectivity and is 2.8 times more infectious than the already existing Delta variant.[32] After previously approved MAbs showed decreased efficacy against the Omicron variant, their emergency use authorizations were removed. Sotrovimab, the only authorized MAb is effective against this variant. Another new monoclonal antibody Bebtelovimab recently got an emergency use authorization for the treatment of COVID-19 have evidenced that the same drug also works against omicron variant.[33] Finding drug target and molecule for these emerging variants is a big challenge for the research community.

Omicron and HIV

The mechanism underlying the new SARS-CoV-2 variants is hypothesized to be based on intra-host evolution in immune-compromised individuals. When compared to the global population, HIV prevalence in South Africa is 20 times higher among the general population. The infection rate for SARS-CoV-2 is also 5%, compared to 3.5% globally. Therefore, it can be assumed that a larger chunk of the population in South Africa must have been co-infected with HIV and SARS-CoV-2 virus. Weak and less responsive immune system in HIV patients aids in prolongation of other severe infections including COVID-19, allowing the co-infecting pathogens to acquire certain mutations that would enable it to escape the neutralizing factors in the body. This could be a plausible way for the emergence of more infectious variants, as is also observed in case of omicron.[34],[35]

 » Conclusion Top

Omicron variant can trigger global epidemic situation as no existing vaccines show significant protective role against it due to the highly mutated RBD region of spike protein. Therefore, there is a need to develop newer generation vaccines and drugs against this variant as well as highly virulent variants that may emerge in future. The drugs effective against omicron are only for symptomatic management. There is no approved drug available for this variant to up to date. The drugs effective against omicron are only for symptomatic management. There is no approved drug available for this variant to up to date. Furthermore, since omicron variant has been found to be less susceptible towards neutralizing antibodies induced by vaccine shots, and the fact that cases of re-infection are increasing at an explosive rate, it is of utmost importance that, the mutational profile of omicron be well-characterized, in order to understand the factors that might be responsible for its resistivity or sensitivity towards available vaccines.[12] Booster dose of BNT162b2 demonstrated the ability to augment the response of neutralizing antibodies against Omicron variant, as found in the preliminary study by Pfizer.[36] Therefore, the proposal to recommend booster doses of vaccines can be considered as a protective measure till the next generation vaccines are available for use.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Kandeel M, Mohamed MEM, Abd El-Lateef HM, Venugopala KN, El-Beltagi HS. Omicron variant genome evolution and phylogenetics. J Med Virol [Internet] [cited 2021 Dec 17];n/a(n/a). Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.27515.  Back to cited text no. 1
Petersen E, Ntoumi F, Hui DS, Abubakar A, Kramer LD, Obiero C, et al. Emergence of new SARS-CoV-2 Variant of Concern Omicron (B.1.1.529) - highlights Africa's research capabilities, but exposes major knowledge gaps, inequities of vaccine distribution, inadequacies in global COVID-19 response and control efforts. Int J Infect Dis [Internet] 2021 [cited 2021 Dec 10];Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634699/.  Back to cited text no. 2
Ferré VM, Peiffer-Smadja N, Visseaux B, Descamps D, Ghosn J, Charpentier C. Omicron SARS-CoV-2 variant: What we know and what we don't. Anaesth Crit Care Pain Med 2021;100998.  Back to cited text no. 3
Daria S, Bhuiyan MA, Islam MdR. Detection of highly muted coronavirus variant Omicron (B.1.1.529) is triggering the alarm for South Asian countries: Associated risk factors and preventive actions. J Med Virol [Internet] [cited 2021 Dec 17];n/a(n/a). Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.27503.  Back to cited text no. 4
Miller NL, Clark T, Raman R, Sasisekharan R. Insights on the mutational landscape of the SARS-CoV-2 Omicron variant receptor binding domain. Cell Reports Medicine. 2022 Jan 24:100527.  Back to cited text no. 5
2nd Global consultation on assessing the impact of SARS-CoV-2 Variants of Concern on Public Health Interventions [Internet]. [cited 2021 Dec 10];Available from: https://www.who.int/publications/m/item/2nd-global-consultation-on-assessing-the-impact-of-sars-cov-2-variants-of-concern-on-public-health-interventions.  Back to cited text no. 6
Vaughan A. Omicron emerges. New Sci 1971 2021;252:7.  Back to cited text no. 7
Saxena SK, Kumar S, Ansari S, Paweska JT, Maurya VK, Tripathi AK, et al. Characterization of the novel SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern and its global perspective. J Med Virol 2021.  Back to cited text no. 8
Prajapat M, Handa V, Sarma P, Prakash A, Kaur H, Sharma S, et al. Update on geographical variation and distribution of SARS-nCoV-2: A systematic review. Indian J Pharmacol 2021;53:310–6.  Back to cited text no. 9
[PUBMED]  [Full text]  
Damavandi PT. The Omicron variant and potential predictions of secondary infections [Internet]. 2021 [cited 2021 Dec 10];Available from: https://osf.io/urt6e/.  Back to cited text no. 10
Venkatakrishnan AJ, Anand P, Lenehan PJ, Suratekar R, Raghunathan B, Niesen MJM, et al. Omicron variant of SARS-CoV-2 harbors a unique insertion mutation of putative viral or human genomic origin [Internet]. 2021 [cited 2021 Dec 10];Available from: https://osf.io/f7txy/.  Back to cited text no. 11
Qin S, Cui M, Sun S, Zhou J, Du Z, Cui Y, et al. Genome Characterization and Potential Risk Assessment of the Novel SARS-CoV-2 Variant Omicron (B.1.1.529). Zoonoses [Internet] 2021 [cited 2021 Dec 10];Available from: https://ucl.scienceopen.com/hosted-document?doi=10.15212/ZOONOSES-2021-0024.  Back to cited text no. 12
Chen J, Wang R, Gilby NB, Wei G-W. Omicron (B.1.1.529): Infectivity, vaccine breakthrough, and antibody resistance. ArXiv 2021;arXiv:2112.01318v1.  Back to cited text no. 13
Kannan SR, Spratt AN, Sharma K, Chand HS, Byrareddy SN, Singh K. Omicron SARS-CoV-2 variant: Unique features and their impact on pre-existing antibodies. J Autoimmun 2022;126:102779.  Back to cited text no. 14
Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern [Internet]. [cited 2021 Dec 10];Available from: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern.  Back to cited text no. 15
Prajapat M, Sarma P, Shekhar N, Prakash A, Avti P, Bhattacharyya A, et al. Update on the target structures of SARS-CoV-2: A systematic review. Indian J Pharmacol 2020;52:142-9.  Back to cited text no. 16
  [Full text]  
Kumar S, Sarma P, Kaur H, Prajapat M, Bhattacharyya A, Avti P, et al. Clinically relevant cell culture models and their significance in isolation, pathogenesis, vaccine development, repurposing and screening of new drugs for SARS-CoV-2: a systematic review. Tissue Cell 2021;70:101497.  Back to cited text no. 17
Prajapat M, Sarma P, Shekhar N, Avti P, Sinha S, Kaur H, et al. Drug targets for corona virus: A systematic review. Indian J Pharmacol 2020;52:56-65.  Back to cited text no. 18
Prajapat M, Shekhar N, Sarma P, Avti P, Singh S, Kaur H, et al. Virtual screening and molecular dynamics study of approved drugs as inhibitors of spike protein S1 domain and ACE2 interaction in SARS-CoV-2. J Mol Graph Model 2020;101:107716.  Back to cited text no. 19
Bhattacharyya A, Kumar S, Sarma P, Kaur H, Prajapat M, Shekhar N, et al. Safety and efficacy of lopinavir/ritonavir combination in COVID-19: A systematic review, meta-analysis, and meta-regression analysis. Indian J Pharmacol 2020;52:313-23.  Back to cited text no. 20
[PUBMED]  [Full text]  
Improved binding affinity of the Omicron's spike protein with hACE2 receptor is the key factor behind its increased virulence | bioRxiv [Internet]. [cited 2022 Jan 22];Available from: https://www.biorxiv.org/content/10.1101/2021.12.28.474338v1.  Back to cited text no. 21
Ali F, Kasry A, Amin M. The new SARS-CoV-2 strain shows a stronger binding affinity to ACE2 due to N501Y mutant. Med Drug Discov 2021;10:100086.  Back to cited text no. 22
Gao S-J, Guo H, Luo G. Omicron variant (B.1.1.529) of SARS-CoV-2, a global urgent public health alert! J Med Virol [Internet] [cited 2021 Dec 10];n/a(n/a). Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.27491.  Back to cited text no. 23
Lu L, Mok BW-Y, Chen L-L, Chan JM-C, Tsang OT-Y, Lam BH-S, et al. Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients. Clin Infect Dis Off Publ Infect Dis Soc Am 2021;ciab1041.  Back to cited text no. 24
Meo SA, Meo AS, Al-Jassir FF, Klonoff DC. Omicron SARS-CoV-2 new variant: global prevalence and biological and clinical characteristics. Eur Rev Med Pharmacol Sci 2021;25:8012-8.  Back to cited text no. 26
What's New [Internet]. COVID-19 Treat. Guidel. [cited 2022 Mar 2];Available from: https://www.covid19treatmentguidelines.nih.gov/about-the-guidelines/whats-new/.  Back to cited text no. 27
Therapeutics and COVID-19: living guideline [Internet]. [cited 2022 Mar 2];Available from: https://www.who.int/publications-detail-redirect/WHO-2019-nCoV-therapeutics-2022.1.  Back to cited text no. 28
Sharma DL. Clinical Guidance for Management of Adult COVID-19 Patients (Revised: 14/01/2022). :1.  Back to cited text no. 29
Update on Omicron [Internet]. [cited 2021 Dec 25];Available from: https://www.who.int/news/item/28-11-2021-update-on-omicron.  Back to cited text no. 30
Commissioner O of the. Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults [Internet]. FDA2021 [cited 2022 Mar 3];Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain.  Back to cited text no. 31
Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19) - PubMed [Internet]. [cited 2022 Mar 2];Available from: https://pubmed.ncbi.nlm.nih.gov/34033342/.  Back to cited text no. 32
Fact Sheet for Healthcare Providers: Emergency Use Authorization for Bebtelovimab. :21.  Back to cited text no. 33
Weigang S, Fuchs J, Zimmer G, Schnepf D, Kern L, Beer J, et al. Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants. Nat Commun 2021;12:6405.  Back to cited text no. 34
Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection | medRxiv [Internet]. [cited 2022 Jan 12];Available from: https://www.medrxiv.org/content/10.1101/2021.06.03.21258228v1.  Back to cited text no. 35
Callaway E. Omicron likely to weaken COVID vaccine protection. Nature 2021;600(7889):367-8.  Back to cited text no. 36


  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 Effect of nasal irrigation in adults infected with Omicron variant of COVID-19: A quasi-experimental study
Li Liu, Shuangshuang Xie, Cheng Li, Liang Su, Chengbao Zhu
Frontiers in Public Health. 2023; 10
[Pubmed] | [DOI]
2 Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2?
Manish Dhawan, AbdulRahman A. Saied, Saikat Mitra, Fahad A. Alhumaydhi, Talha Bin Emran, Polrat Wilairatana
Biomedicine & Pharmacotherapy. 2022; : 113522
[Pubmed] | [DOI]


Print this article  Email this article


Site Map | Home | Contact Us | Feedback | Copyright and Disclaimer | Privacy Notice
Online since 20th July '04
Published by Wolters Kluwer - Medknow