Review Article

SARS-COV-2 Notable Mutations and Variants: A Review Article


SARS-COV-2 (COVID-19) the virus that caused an epidemic of sever acute respiratory syndrome is what the world has been dealing with since Dec 2019. As the pandemic continues different variants that emerge during mutations have become the latest concern, with notable examples detected in South Africa, Brazil, and UK. Variants are complicated and each one is a collection of several mutations, all of which have the potential to change the virus in unexpected ways. Studying variants is imperative as they can lead the epidemic to the increase of population immunity. In the present study, we reviewed key mutations and concerning variants according to the WHO tracking Sars-Cov-2 program. Databases were searched through Feb to Mar 2022. Overall, 477 studies were extracted from databases, among them 165 studies included mutations, 239 included COVID-19 variants and 43 included both mutations and variants. At the final step of data screening 24 studies associated to mutations, 31 studies with the highlighted information on COVID-19 variants and 31 studies related to both mutations and variants were extracted for this review article. In conclusion, analyses of the genomic sequence of SARS-CoV-2 indicate that structural proteins are key molecules in the assembly of virus while NSPs can have different biochemical properties and possibly cellular functions.

1. Zhu N, Zhang D, Wang W, et al (2020). A Novel Coronavirus from Patients with Pneumonia in China. N Engl J Med, 382(8): 727-733.
2. Farhud DD, Bahadori M, Zarif-Yeganeh M (2021). Evidence of the Ancestries of COVID-19 Virus in East Asia, More than 20,000 Years Ago. Iran J Public Health, 50(9): i-v.
3. Enard D, Petrov DA (2020). Ancient RNA virus epidemics through the lens of recent adaptation in human genomes. Philosophical Transactions of The Royal Society B Biological Sciences, 375(1812): 20190575.
4. Farhud DD, Azari M, Mehrabi A (2022). The History of Corona Virus, from Neanderthals to the Present Time: A Brief Review. Iran J Public Health, 51(3): 531-534.
5. Al-Osail AM, Al-Wazzah MJ (2017). The history and epidemiology of Middle East respiratory syndrome corona virus. Multidiscip Respir Med, 12:20.
6. Farhud DD, Zokaei S (2020). Fight against Viruses (COVID-19): Peace among Nations. Iran J Public Health, 49(Suppl 1):1-3.
7. Ullah H, Ullah A, Gul A, et al (2021). Novel coronavirus 2019 (COVID-19) pandemic outbreak: A comprehensive review of the current literature. Vacunas, 22(2): 106-113.
8. Tsabouri S, Makis A, Kosmeri C, et al (2021). Risk Factors for Severity in Children with Coronavirus Disease 2019: A Comprehensive Literature Review. Pediatr Clin North Am. 68(1): 321-338.
9. Wu A, Peng Y, Huang B, et al (2020). Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe, 27(3): 325-328.
10. Huang Y, Yang C, Xu XF, et al (2020). Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacologica Sinica, 41(9):1141-1149.
11. Malone B, Urakova N, Snijder EJ, et al (2022). Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design. Nat Rev Mol Cell Biol, 23(1): 21-39.
12. Antony P, Vijayan R (2021). Role of SARS-CoV-2 and ACE2 variations in COVID-19. Biomed J, 44(3): 235-244.
13. Belouzard S, Millet JK, Licitra BN, et al (2012). Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses, 4(6): 1011-33.
14. Brobst B, Borger J (2022). Benefits And Risks Of Administering Monoclonal Antibody Therapy For Coronavirus (COVID-19). StatPearls. Treasure Island (FL), pp.: 6-8.
15. Cheng Y, He B, Yang J, et al (2019). Crystal structure of the S1 subunit N-terminal domain from DcCoV UAE-HKU23 spike protein. Virology, 535: 74-82.
16. Becerra-Flores M, Cardozo T (2020). SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate. Int J Clin Pract, 74(8): e13525.
17. Korber B, Fischer WM, Gnanakaran S, et al (2020). Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell, 182(4):812-827 .
18. Jackson CB, Zhang L, Farzan M, Choe H (2021). Functional importance of the D614G mutation in the SARS-CoV-2 spike protein. Biochem Biophys Res Commun, 538:108-115.
19. Zhang L, Jackson CB, Mou H, et al (2020). The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv, doi: 10.1101/2020.06.12.148726.
20. Zhu X, Mannar D, Srivastava SS, et al (2021). Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. PLoS Biol, 19(4):e3001237.
21. Tang JW, Toovey OTR, Harvey KN, et al (2021). Introduction of the South African SARS-CoV-2 variant 501Y.V2 into the UK. J Infect, 82(4): e8-e10.
22. Tian F, Tong B, Sun L, et al (2021). N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2. Elife, 10:e69091.
23. Tegally H, Wilkinson E, Giovanetti M, et al (2021). Detection of a SARS-CoV-2 variant of concern in South Africa. Nature, 592(7854):438-443.
24. Yang WT, Huang WH, Liao TL, et al (2022). SARS-CoV-2 E484K Mutation Narrative Review: Epidemiology, Immune Escape, Clinical Implications, and Future Considerations. Infect Drug Resist, 15:373-385.
25. Ding C, He J, Zhang X, et al (2021). Crucial Mutations of Spike Protein on SARS-CoV-2 Evolved to Variant Strains Escaping Neutralization of Convalescent Plasmas and RBD-Specific Monoclonal Antibodies. Front Immunol, 12:693775.
26. Jangra S, Ye C, Rathnasinghe R, et al (2021). The E484K mutation in the SARS-CoV-2 spike protein reduces but does not abolish neutralizing activity of human convalescent and post-vaccination sera. medRxiv, doi: 10.1101/2021.01.26.21250543.
27. Tao K, Tzou PL, Nouhin J, et al (2021). The biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet, 22(12): 757-773.
28. Choi B, Choudhary MC, Regan J, et al (2020). Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. N Engl J Med, 383(23):2291-2293.
29. Gangavarapu K, Latiff AA, Mullen JL, et al (2022). Outbreak. info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations. medRxiv, doi:
30. Hodcroft EB, Domman DB, Snyder DJ, et al (2021). Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677. medRxiv, doi: 10.1101/2021.02.12.21251658.
31. Lubinski B, Fernandes MHV, Frazier L, et al (2021). Functional evaluation of the P681H mutation on the proteolytic activation the SARS-CoV-2 variant B.1.1.7 (Alpha) spike. bioRxiv, doi: 10.1101/2021.04.06.438731.
32. Kim Y, Gaudreault NN, Meekins DA, et al (2021). Effects of Spike Mutations in SARS-CoV-2 Variants of Concern on Human or Animal ACE2-Mediated Virus Entry and Neutralization. bioRxiv, doi: 10.1101/2021.08.25.457627.
33. Luo CH, Morris CP, Sachithanandham J, Amadi A, et al (2021). Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals. medRxiv, doi: 10.1101/2021.08.15.21262077.
34. Volz E, Mishra S, Chand M, et al (2021). Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature, 593(7858): 266-269.
35. Choi JY, Smith DM (2021). SARS-CoV-2 Variants of Concern. Yonsei Med J, 62(11): 961-968.
36. Cascella M, Rajnik M, Aleem A, et al (2022). Features, Evaluation, and Treatment of Coronavirus (COVID-19). StatPearls. Treasure Island (FL).P.:11-12
37. Ramesh S, Govindarajulu M, Parise RS, et al (2021). Emerging SARS-CoV-2 variants: A review of its mutations, its implications and vaccine efficacy. Vaccines (Basel), 9(10):1195.
38. Shiehzadegan S, Alaghemand N, Fox M, et al (2021). Analysis of the Delta Variant B.1.617.2 COVID-19. Clin Pract, 11(4):778-784.
39. Menni C, Valdes AM, Polidori L, et al (2022). Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study. Lancet, 399(10335): 1618-24.
40. Mohammadi M, Shayestehpour M, Mirzaei H (2021). The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines. Braz J Infect Dis, 25(4):101606.
41. Cao Y, Wang J, Jian F, et al (2022). Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature, 602(7898):657-663.
42. Mallapaty S (2022). Where did Omicron come from? Three key theories. Nature, 602(7895):26-8.
43. Callaway E (2021). Heavily mutated Omicron variant puts scientists on alert. Nature, 600(7887):21.
44. Bhattacharyya RP, Hanage WP (2022). Challenges in inferring intrinsic severity of the SARS-CoV-2 Omicron variant. N Engl J Med, 386(7):e14.
45. Abbasi J (2021). Researchers tie severe immunosuppression to chronic COVID-19 and virus variants. JAMA, 325(20):2033-2035.
46. Pal M, Berhanu G, Desalegn C, et al (2020). Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update. Cureus, 12(3):e7423.
47. Farhud DD, Zokaei SH (2021). A Brief Overview of COVID-19 Vaccines. Iran J Public Health, 50(7):i-vi.
IssueVol 51 No 7 (2022) QRcode
SectionReview Article(s)
COVID 19 SARS-COV-2 Mutations Concerning variants

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Farhud D, Mojahed N. SARS-COV-2 Notable Mutations and Variants: A Review Article. Iran J Public Health. 2022;51(7):1494-1501.