Mohd Fardeen Husain SHAHANSHAH, Saloni JAİN, Bhawna SHARMA, Ananya GREWALL, Shalini SWAMİ

Comparative Analysis of B.1.617.2 (Delta) Variant of SARS-CoV-2

ABSTRACT The emergence of numerous variants of SARS-CoV-2 has caused massive setbacks and prolonged the COVID-19 pandemic. Some of the variants are still under investigation, while some have become a reason of grave concern. One such variant is B.1.617.2, known as the Delta variant, which was first detected in India. A comprehensive analysis and comparison of this particular variant have been done to the original Wuhan strain, and the possible reasons behind rapid mutation have also been discussed. A comprehensive literature search was done to summarize the information on the variants of SARS-CoV-2 and the reasons behind their mutation, with a significant focus on the B.1.617.2 variant. Data were collected from various online sources such as PubMed, Google Scholar, MEDLINE, Worldometer, WHO, CDC, and GISAID. In addition, 3D structures of spike proteins were obtained from Protein Data Bank (PDB). The data shows that the spike protein of the B.1.617.2 strain is highly mutated and has accumulated eight amino acid changes. Besides spike protein, changes in non-structural proteins (nsP2, nsP3, nsP4, nsP12, and nsP15), other structural proteins (nucleocapsid and membrane protein), and accessory proteins (ns3, ns7a) have been observed as well. Furthermore, in almost all the variants of SARS-CoV-2, D614G mutation occurs, suggesting its role in increased infectivity and transmission. New variants are continuously emerging on which we have no control. Spike mutations are more favored and essential in the evolution of new variants because it increases the transmissibility and infectivity of the virus. Therefore, to maximally protect public health, knowledge of different variants is essential. J Microbiol Infect Dis 2022; 12(1):38-51.

Keywords:

SARS-CoV-2, Spike, Mutation, Variants, B.1.617.2 variant,

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1. Kaur SP, Gupta V. COVID-19 Vaccine: A comprehensive status report. Virus Research. 2020;198114. doi:10.1016/j.virusres.2020.198114
2. Sharma B, Shahanshah MF, Gupta S, Gupta V. Recent advances in the diagnosis of COVID-19: A bird’s eye view. Expert Rev Mol Diagn. 2021;21(5):475-491. doi:10.1080/14737159.2021.1874354
3. Worldometer. COVID live update: 168,291,956 cases and 3,493,098 deaths from the Coronavirus. Available: https://www.worldometers.info/coronavirus/. (Accessed on May 25, 2021).
4. WHO Coronavirus (COVID-19) Dashboard. Available: https://covid19.who.int/. (Accessed on May 25, 2021).
5. Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020;10(5):766-788. doi:10.1016/j.apsb.2020.02.008
6. Wu A, Peng Y, Huang B, et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe 2020; 27(3):325-328. doi:10.1016/j.chom.2020.02.001
7. Giovanetti M, Benedetti F, Campisi G, et al. Evolution patterns of SARS-CoV-2: Snapshot on its genome variants. Biochem Biophys Res Commun 2021; 538;88-91. doi:10.1016/j.bbrc.2020.10.102
8. Singh A, Gupta V. SARS-CoV-2 therapeutics: how far do we stand from a remedy? Pharmacol Rep 2021;73(3):750-768. doi:10.1007/s43440-020-00204-0
9. Dolan PT, Whitfield ZJ, Andino R. Mechanisms and Concepts in RNA Virus Population Dynamics and Evolution. Annu Rev Virol 2018; 5(1):69-92. doi:10.1146/annurev-virology-101416-041718
10. Sanjuán R, Domingo-Calap P. Mechanisms of viral mutation. Cell Mol Life Sci. 2016; 73(23):4433-4448. doi:10.1007/s00018-016-2299-6
11. SARS-CoV-2 Variant Classifications and Definitions. CDC; 2021. Available: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html (Accessed on May 16, 2021.)
12. What Mutations of SARS-CoV-2 are Causing Concern? 2021. Available: https://www.news-medical.net/health/What-Mutations-of-SARS-CoV-2-are-Causing-Concern.aspx. (Accessed on May 16, 2021).
13. Beskrivelse af udvalgte virus varianter. Statens Serum Institut (SSI); 2021. Available: https://covid19.ssi.dk/virusvarianter/virusvariantbeskrivelser. (Accessed on May 16, 2021).
14. Annavajhala MK, Mohri H, Zucker JE, et al. A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York. medRxiv. February 2021. doi:10.1101/2021.02.23.21252259
15. Pfizer and Moderna vaccines effective against new NYC variant. Science X staff, Medical Xpress; 2021. Available: https://medicalxpress.com/news/2021-04-pfizer-moderna-vaccines-effective-nyc.html. (Accessed on May 16, 2021).
16. VDH (Virginia Department of Health); 2021 Available: https://www.vdh.virginia.gov/content/uploads/sites/8/2021/04/PartnerCall_Update_SARS-CoV-2_VariantsofConcern_04.30.2021. (Accessed May on 16, 2021).
17. Hoffmann M, Hofmann-Winkler H, Krüger N, et al. SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination. bioRxiv.2021:442663. doi:10.1101/2021.05.04.442663
18. Cherian S, Potdar V, Jadhav S, et al. Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India. bioRxiv.2021:440932. doi:10.1101/2021.04.22.440932
19. Yadav PD, Sapkal GN, Abraham P, et al. Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. bioRxiv.2021:441101. doi:10.1101/2021.04.23.441101
20. Fox News; 2021 Available: https://www.foxnews.com/health/pfizer-moderna-covid-19-vaccines-indian-coronavirus-variant-emory. (Accessed on May 16, 2021).
21. RIVM; 2021. Available: https://www.rivm.nl/en/news/brazilian-coronavirus-variants-p1-and-p2-found-in-netherlands. (Accessed on May 16, 2021).
22. Racaniello V. SARS-CoV-2 variant B.1.1.7 is not more virulent;2021. Available: https://www.virology.ws/2021/04/15/sars-cov-2-variant-b117-is-not-more-virulent/. (Accessed on May 25, 2021).
23. Wang P, Casner RG, Nair MS, et al. Increased resistance of SARS-CoV-2 variant P. 1 to antibody neutralization. Cell Host & Microbe 2021; 29(5):747-751. doi:10.1101/2021.01.25.428137
24. Shen X, Tang H, McDanal C, Wagh K, Fischer W, Theiler J, Yoon H, Li D, Haynes BF, Sanders KO, Gnanakaran S. SARS-CoV-2 variant B. 1.1. 7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell host & microbe. 2021; 29(4):529-539. doi:10.1101/2021.01.27.428516
25. Edara VV, Floyd K, Lai L, et al. Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant. medRxiv. 2021.doi:10.1101/2021.02.02.21250799
26. Wang P, Casner RG, Nair MS, et al. Increased resistance of SARS-CoV-2 variant P. 1 to antibody neutralization. Cell host & microbe. 2021;29(5):747-51.doi:10.1101/2021.03.01.433466
27. Planas D, Bruel T, Grzelak L, et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med. 2021;27(5):917-924. doi:10.1038/s41591-021-01318-5
28. Deng X, Garcia-Knight MA, Khalid MM, et al. Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. MedRxiv. 2021.doi:10.1101/2021.03.07.21252647
29. Doucleff M. People Are Talking About A “Double Mutant” Variant In India. What Does That Mean? NPR 2021. Available: https://www.npr.org/sections/goatsandsoda/2021/04/24/988744811/people-are-talking-about-a-double-mutant-variant-in-india-what-does-that-mean.. (Accessed May 16, 2021).
30. SARS-CoV-2 variants of concern as of 29 November 2021. ECDC 2021. Available: https://www.ecdc.europa.eu/en/covid-19/variants-concern. (Accessed November 30, 2021).
31. Callaway E., Heavily mutated Omicron variant puts scientists on alert. Nature. 2021.DOI: https://doi.org/10.1038/d41586-021-03552-w (Accessed on 29 November 2021)
32. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. World Health Organisation.2021. https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern (Accessed on 29 November 2021)
33. Implications of the emergence and spread of the SARS-CoV-2 B.1.1.529 variant of concern (Omicron) for the EU/EEA. Threat Assessment Brief, European Center for Disease Prevention and Control. 2021. Available: https://www.ecdc.europa.eu/
34. Jerusalem Post Staff. New coronavirus variant identified in Europe. The Jerusalem Post 2021. Available: https://www.jpost.com/. (Accessed May 25, 2021).
35. GitHub. cov-lineages/pango-designation. 2021. Available: https://github.com/cov-lineages/pango-designation.(Accessed May 25, 2021).
36. Jangra S, Ye C, Rathnasinghe R, et al. SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. The Lancet Microbe 2021.doi:10.1016/S2666-5247(21)00068-9
37. Bugembe DL, Phan MV, Ssewanyana I, et al. A SARS-CoV-2 lineage A variant (A. 23.1) with altered spike has emerged and is dominating the current Uganda epidemic. MedRxiv. 2021.doi:10.1101/2021.02.08.21251393
38. A coronavirus variant, with a “similar change” to the fast-spreading variant in the UK and US, has emerged in Uganda. Business Insider India 2021. Available: https://www.businessinsider.in/science/health/news/a-coronavirus-variant-with-a-similar-change-to-the-fast-spreading-variant-in-the-uk-and-us-has-emerged-in-uganda/articleshow/80881380.cms.(Accessed May 25, 2021).
39. Mallm JP, Bundschuh C, Kim H, et al. Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein. medRxiv. 2021.doi:10.1101/2021.04.27.21254849
40. SARS-CoV-2 variants of concern and variants under investigation in England. PHE 2021. Available: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/984274/Variants_of_Concern_VOC_Technical_Briefing_10_England.pdf.(Accessed May 25, 2021).
41. C.37, the new variant of COVID-19 that spreads in Peru and Chile | coronavirus | INS | UPCH | PERU. ARCHYDE 2021. Available: https://www.archyde.com/c-37-the-new-variant-of-covid-19-that-spreads-in-peru-and-chile-coronavirus-ins-upch-peru/. (Accessed May 25, 2021).
42. Tegally H, Wilkinson E, Giovanetti M, et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature. 2021;592(7854):438-443. doi:10.1038/s41586-021-03402-9
43. Cele S, Gazy I, Jackson L, et al. Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature. 2021;593(7857):142-146. doi:10.1038/s41586-021-03471-w
44. Estimates of severity and transmissibility of novel South Africa SARS-CoV-2 variant 501Y.V2. GitHub 2021. Available: https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA. (Accessed May 25, 2021).
45. Davies NG, Abbott S, Barnard RC, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science. 2021;372(6538). doi:10.1126/science.abg3055
46. Davies NG, Jarvis CI, CMMID COVID-19 Working Group, et al. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature. 2021;593(7858):270-274. doi:10.1038/s41586-021-03426-1
47. CoVsurver Analysis of the sequences. GISAID. Available: https://www.gisaid.org/. (Accessed Nov 29, 2021).