Diversity due to mutations in circulating virus strains of SARSCoV-2 may delay control of COVID-19

Sharanagouda S. Patil Chandan Shivamallu Chandan Dharmashekara Sushma Pradeep Kuralayanapalya Puttahonnappa Suresh Ashwini Prasad Shiva Prasad Kollur Mahendra P. Yadav Chandrashekar Srinivasa Bramhadev Pattnaik   

Open Access   

Published:  Jan 05, 2022


Severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) is a beta-coronavirus (beta- CoV; sarbecovirus), like its predecessors SARS and MERS CoVs. Of the structural proteins of the virus, the Spike (S) protein on the virion envelope binds to the host cell ACE2 through viral epitopes in the receptor-binding domain (RBD). Deletions in the ORF8 as well as mutations in the S gene of SARS-CoV of 2003 were related to adaptation of the virus to humans. The emergence of novel variants of SARS-CoV-2, viz., B.1.1.7, B.1.427 and B.1.429, B.1.617 and its Kappa and Delta strains/ variants, B.1.351, and P.1 in the United Kingdom, Americas, India, South Africa and Brazil, respectively, has been found be associated with the current waves of the COVID-19 pandemic. These variants are antigenically dissimilar, whereas the current COVID-19 vaccines are monovalent. This is a handicap in the control program. The Delta variant has been reported in 74 countries as of 14 June 2021 and the anticipated third wave involving this variant is of concern to the countries (www.gavi.org). Of late, on 17 June 2021, Delta Plus variant was identified in India (AIIMS, Bhopal, India). Circulation of virus in vaccinated population may lead to endemicity, and this can be monitored by regular serosurveillance for antibodies against select non-structural proteins (NSPs) of the virus; antibodies to NSPs will indicate virus replication in the host. Endemic areas will have higher NSP reactors. It is predicted that the Delta B.1 variant may ignite the third wave of the disease in many countries. As it has been difficult to achieve uniformity in time and density of the vaccination even in the districts, circulation of the virus in partially immune population may lead to the selection of newer variants of SARS-CoV-2. The presence of monoclonal antibody resistant mutants and neutralization—escape mutants in quasispecies structure of another + sense RNA virus, i.e., Aphthovirus (FMD virus; foot and mouth disease virus) in the family Picornaviridae is well documented. The situation could be similar in the Coronaviridae member SARS-CoV-2. Previous immunity may not protect against current/ future mutants thereby pro-longing the COVID-19 control Programme

Keyword:     SARS-CoV-2 COVID-19 RNA viruses Quasispecies neutralization escape mutants Non-structural proteins Serosurveillance DIVA/ DIVI.


Patil SS, Shivamallu C, Dharmashekara C, Pradeep S, Suresh KP, Ashwini Prasad, Kollur SP, Yadav MP, Chandrashekar Srinivasa, Pattnaik B. Diversity due to mutations in circulating virus strains of SARS-CoV-2 may delay control of COVID-19. J Appl Biol Biotech, Online First.

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

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1.Nuthalapati P, Ghanta MK, Natesh NS, Bhaskar LVKS. Association of hypercoagulation with severe acute respiratory syndrome coronavirus 2 infection. Blood Res 2021;56 (2):61-4. https://doi.org/10.5045/br.2021.2021011

2. Ghorbani A, Samarfard S, Ramezani A, Izadpanah K, Afsharifar A, Eskandari, MH, et al. Quasi-species nature and differential gene expression of severe acute respiratory syndrome coronavirus 2 and phylogenetic analysis of a novel Iranian strain. Infect Genet Evol 2020;85:104556. https://doi.org/10.1016/j.meegid.2020.104556

3. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395(10224):565-74. https://doi.org/10.1016/S0140-6736(20)30251-8

4. Phan T. Genetic diversity and evolution of SARS-CoV-2. Infect Genet Evol 2020;81:104260. https://doi.org/10.1016/j.meegid.2020.104260

5. Kim SJ, Nguyen VG, Park YH, Park BK, Chung HC. A novel synonymous mutation of SARS-CoV-2: is this possible to affect their antigenicity and immunogenicity? Vaccines 2020;8(2):220. https://doi.org/10.3390/vaccines8020220

6. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579(7798):265-9. https://doi.org/10.1038/s41586-020-2008-3

7. Loeffelholz MJ, Tang YW. Laboratory diagnosis of emerging human coronavirus infections-the state of the art. Emerg Microbes Infect 2020;9(1):747-56. https://doi.org/10.1080/22221751.2020.1745095

8. Chan JFW, Kok KH, Zhu Z, Chu H, To KKW, Yuan S, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 2020;9(1):221-36. https://doi.org/10.1080/22221751.2020.1719902

9. Liu X, Zhang B, Jin Z, Yang H, Rao Z. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature 2020;582(7811):289-93. https://doi.org/10.1038/s41586-020-2223-y

10. Chitranshi N, Gupta VK, Rajput R, Godinez A, Pushpitha K, Shen T, et al. Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL pro targeting repurposed drug candidates. J Transl Med 2020;18(1):1-15. https://doi.org/10.1186/s12967-020-02448-z

11. Dharmashekara C, Pradeep S, Prasad SK, Jain AS, Syed A, Prasad KS, et al. Virtual screening of potential phyto-candidates as therapeutic leads against SARS-CoV-2 infection. Environ Challs 2021;100136. https://doi.org/10.1016/j.envc.2021.100136

12. Sanchez-Morgado JM, Poynter S, Morris TH. Molecular characterization of a virulent canine coronavirus BGF strain. Virus Res 2004;104(1):27-31. https://doi.org/10.1016/j.virusres.2004.02.038

13. Drosten C, Günther S, Preiser W, Van Der Werf S, Brodt HR, Becker S, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 2003;348(20):1967-76. https://doi.org/10.1056/NEJMoa030747

14. Cyranoski D. Mystery deepens over animal source of coronavirus. Nature 2020;579(7797):18-20. https://doi.org/10.1038/d41586-020-00548-w

15. Chu H, Chan JFW, Yuen TTT, Shuai H, Yuan S, Wang Y, et al. Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Lancet Microbe 2020;1(1):e14-23.18. https://doi.org/10.1016/S2666-5247(20)30004-5

16. Jarvis, M.C. Aerosol transmission of SARS-CoV-2: physical principles and implications. Front Public Health 2020;8: 813. https://doi.org/10.3389/fpubh.2020.590041

17. Mishra SK, Tripathi T. One year update on the COVID-19 pandemic: where are we now? Acta Trop 2021;105778. https://doi.org/10.1016/j.actatropica.2020.105778

18. Cao C, He L, Tian Y, Qin Y, Sun H, Ding W, et al. Molecular epidemiology analysis of early variants of SARS-CoV-2 reveals the potential impact of mutations P504L and Y541C (NSP13) in the clinical COVID-19 outcomes. Infect Genet Evol 2021;92:104831. https://doi.org/10.1016/j.meegid.2021.104831

19. Winger A, Caspari T. The spike of concern-the novel variants of SARS-CoV-2. Viruses 2020;13(6):1002. https://doi.org/10.3390/v13061002

20. Phan T. Novel coronavirus: from discovery to clinical diagnostics. Infect Genet Evol 2020;79:104211. https://doi.org/10.1016/j.meegid.2020.104211

21. Hassan SS, Aljabali AA, Panda PK, Ghosh S, Attrish D, Choudhury PP, et al. A unique view of SARS-CoV-2 through the lens of ORF8 protein. Comput Biol Med 2021;133:104380. https://doi.org/10.1016/j.compbiomed.2021.104380

22. Grubaugh ND, Petrone ME, Holmes EC. We shouldn't worry when a virus mutates during disease outbreaks. Nat Microbiol 2020;5:529-30. https://doi.org/10.1038/s41564-020-0690-4

23. Lauring AS, Hodcroft AB. Genetic variants of SARS-CoV-2-what do they mean? JAMA 2021;325:529-31. https://doi.org/10.1001/jama.2020.27124

24. Singh PK, Kulsum U, Rufai SB, Mudliar SR, Singh S. Mutations in SARS-CoV-2 leading to antigenic variations in spike protein: a challenge in vaccine development. J Lab Physicians 2020;12(2):154. https://doi.org/10.1055/s-0040-1715790

25. Roncati L, Palmieri B. What about the original antigenic sin of the humans versus SARS-CoV-2? Med Hypotheses 2020;142:109824. https://doi.org/10.1016/j.mehy.2020.109824

26. Majumdar P, Niyogi S. ORF3a mutation associated with higher mortality rate in SARS-CoV-2 infection. Epidemiol Infect 2020;148:e262. https://doi.org/10.1017/S0950268820002599

27. van Dorp L, Acman M, Richard D, Shaw LP, Ford CE, Ormond L, et al. Emergence of genomic diversity and recurrent mutations in SARSCoV-2. Infect Genet Evol 2020;83:104351. https://doi.org/10.1016/j.meegid.2020.104351

28. Wang C, Liu Z, Chen Z, Huang X, Xu M, He T, et al. The establishment of reference sequence for SARS-CoV-2 and variation analysis. J Med Virol 2020;92(6):667-74. https://doi.org/10.1002/jmv.25762

29. Yin, C. Genotyping coronavirus SARS-CoV-2: methods and implications. Genomics 2020;112(5):3588-96. https://doi.org/10.1016/j.ygeno.2020.04.016

30. Nguyen TT, Pham TN, Van TD, Nguyen TT, Nguyen DTN, Le HNM, et al. Genetic diversity of SARS-CoV-2 and clinical, epidemiological characteristics of COVID-19 patients in Hanoi, Vietnam. PLoS One 2020;15(11):e0242537. https://doi.org/10.1371/journal.pone.0242537

31. Su YC, Anderson DE, Young BE, Linster M, Zhu F, Jayakumar J, et al. Discovery and genomic characterization of a 382-nucleotide deletion in ORF7b and ORF8 during the early evolution of SARS-CoV-2. MBio 2020;11(4):e01610-20. https://doi.org/10.1128/mBio.01610-20

32. Tang JW, Tambyah PA, Hui DS. Emergence of a new SARS-CoV-2 variant in the UK. J Infect 2020;82(4):e27-8. https://doi.org/10.1016/j.jinf.2020.12.024

33. Islam MR, Hoque MN, Rahman MS. Genome-wide analysis of SARSCoV-2 virus strains circulating worldwide implicates heterogeneity. Sci Rep 2020;10:14004. https://doi.org/10.1038/s41598-020-70812-6

34. Rambaut A, Holmes EC, O'Toole Á. A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nat Microbiol 2020;5:1403-7. https://doi.org/10.1038/s41564-020-0770-5

35. Samuel A, Stéphanie H, Vincent F, Laura V, Sabine T, Emmanuel L, et al. Rapid spread of the SARS-CoV-2 Delta variant in some French regions. Euro Surveill 2021;26:2100573. https://doi.org/10.2807/1560-7917.ES.2021.26.28.2100573

36. Faria NR, Mellan TA, Whittaker C, Claro IM, da S Candido D, Mishra S. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 2021;372:815-21. https://doi.org/10.1126/science.abh2644

37. Janik E, Bartos M, Niemcewicz M, Gorniak L, Bijak M. SARS-CoV-2: outline, Prevention, and Decontamination. Pathogens 2021;10:114. https://doi.org/10.3390/pathogens10020114

38. Sabino EC, Buss LF, Carvalho MPS, Prete Jr CA, Crispim MAE. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet 2021;397:452-5. https://doi.org/10.1016/S0140-6736(21)00183-5

39. Tegally H, Wilkinson E, Giovanetti M. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 2021;592:438-43 . https://doi.org/10.1038/s41586-021-03402-9

40. Majumdar P, Niyogi S. ORF3a mutation associated with higher mortality rate in SARS-CoV-2 infection. Epidemiol Infect 2020;148. https://doi.org/10.1017/S0950268820002599

41. Zhang L, Jackson CB, Mou H, Ojha A, Rangarajan ES, Izard T, Farzan M, Choe, H. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. BioRxiv 2020;11(1):6013. https://doi.org/10.1101/2020.06.12.148726

42. Yadav P, Mohandas S, Sarkale P, Nyayanit D, Shete A, Sahay R, Potdar V, Baradkar S, Gupta N, Sapkal G, Abraham P. Isolation of SARS-CoV-2 B. 1.1. 28.2 P2 variant and pathogenicity comparison with D614G variant in hamster model. BioRxiv 2021. https://doi.org/10.1101/2021.05.24.445424

43. Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B. Ethnic differences in SARS-CoV-2 infection and COVID-19- related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform. Lancet 2021;397:1711-24. https://doi.org/10.1016/S0140-6736(21)00634-6

44. Johnson BA, Xie X, Kalveram B, Lokugamage KG, Muruato A, Zou J, et al. Furin cleavage site is key to SARS-CoV-2 pathogenesis. Nature 2020;591(7849):293-9. https://doi.org/10.1038/s41586-021-03237-4

45. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses The species severe acute respiratory syndromerelated coronavirus: classifying 2019-nCoV and naming it SARSCoV-2. Nat Microbiol 2020;5:536-44. https://doi.org/10.1038/s41564-020-0695-z

46. Vankadari N. Overwhelming mutations or SNPs of SARS-CoV-2: a point of caution. Gene 2020;752:144792. https://doi.org/10.1016/j.gene.2020.144792

47. Debnath M, Banerjee M, Berk M. Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes. FASEB J 2020;34(7):8787-95. https://doi.org/10.1096/fj.202001115R

48. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86(4):1343-6. https://doi.org/10.1172/JCI114844

49. Saab YB, Gard PR, Overall ADJ. The geographic distribution of the ACE II genotype: a novel finding. Genet Res 2007;89(4):259-67. https://doi.org/10.1017/S0016672307009019

50. Aung AK, Aitken T, Teh BM, Yu C, Ofori-Asenso R, Chin KL, et al. Angiotensin converting enzyme genotypes and mortality from COVID-19: an ecological study. J Infect 2020;81(6):961-5. https://doi.org/10.1016/j.jinf.2020.11.012

51. Thuy BTP, My TTA, Hai NTT, Hieu LT, Hoa TT, Thi Phuong Loan H, et al. Investigation into SARS-CoV-2 resistance of compounds in garlic essential oil. ACS Omega 2020;5(14):8312-20. https://doi.org/10.1021/acsomega.0c00772

52. Ellinghau D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, et al. The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis. MedRxiv 2020.

53. Lumley SF, O'Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB, et al. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med 2021;384(6):533-40. https://doi.org/10.1056/NEJMoa2034545

54. Rostami A, Sepidarkish M, Leeflang M, Riahi SM, Shiadeh MN, Esfandyari S, Mokdad AH, Hotez PJ, Gasser RB. SARS-CoV-2 seroprevalence worldwide: a systematic review and meta-analysis. Clin Microbiol Infect 2020;27(3):331-40. https://doi.org/10.1016/j.cmi.2020.10.020

55. Hoffman T, Nissen K, Krambrich J, Rönnberg B, Akaberi D, Esmaeilzadeh M, et al. Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2. Infect Ecol Epidemiol 2020;10(1):1754538. https://doi.org/10.1080/20008686.2020.1754538

56. Hassan SS, Choudhury PP, Roy B. SARS-CoV2 envelope protein: non-synonymous mutations and its consequences. Genomics 2020;112(6):3890-2. https://doi.org/10.1016/j.ygeno.2020.07.001

57. Quinonez E, Vahed M, Shahraki AH, Mirsaeidi M. Structural Analysis of the Novel Variants of SARS-CoV-2 and Forecasting in North America. Viruses 2021; 13(5):930. https://doi.org/10.3390/v13050930

58. Focosi D, Tuccori M, Baj A, Maggi F. SARS-CoV-2 Variants: a synopsis of in vitro efficacy data of convalescent plasma, currently marketed vaccines, and monoclonal antibodies. Viruses 2021;13:1211. https://doi.org/10.3390/v13071211

59. Weisblum Y, Schmidt F, Zhang F, DaSilva J, Poston D, Lorenzi JC, et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife 2020;9:e61312. https://doi.org/10.7554/eLife.61312

60. Kemp SA, Collier DA, Datir R, Ferreira IA, Gayed S, Jahun A, et al. Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation. Nature 2020;592(7853):277-82. https://doi.org/10.1038/s41586-021-03291-y

61. Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 2020;182(4):812-27. https://doi.org/10.1016/j.cell.2020.06.043

62. Kemp SA, Collier DA, Datir R, Ferreira I, Gayed S, Jahun A, et al. Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation. medRxiv [Preprint]. 2020 Dec 29:2020.12.05.20241927. https://doi.org/10.1101/2020.12.05.20241927

63. Domingo E, Perales C. Viral quasispecies. PLoS Genet 2019;15(10): e1008271. https://doi.org/10.1371/journal.pgen.1008271

64. Fenollar F, Mediannikov O, Maurin M, Devaux C, Colson P, Levasseur A, et al. Mink, SARS CoV-2 and the Human-Animal interface. Front Microbiol 2021;12:1-12. https://doi.org/10.3389/fmicb.2021.663815

65. Oude Munnink BB, Sikkema RS, Nieuwenhuijse DF, Molenaar RJ, Munger E, Molenkamp R, et al. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science 2021;371:172-7. https://doi.org/10.1126/science.abe5901

66. Yadav P, Mohandas S, Sarkale P, Nyayanit D, Shete A, Sahay R, et al. Isolation of SARS-CoV-2 B. 1.1. 28.2 P2 variant and pathogenicity comparison with D614G variant in hamster model. BioRxiv 2020. https://doi.org/10.1101/2021.05.24.445424

67. Oreshkova N, Molenaar RJ, Vreman S, Harders F, Munnink BBO, Hakze-van Der Honing RW, et al. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Euro Surveill 2020;25(23):2001005. https://doi.org/10.2807/1560-7917.ES.2020.25.23.2001005

68. Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS- coronavirus 2. Science 2020;368(6494):1016-20. https://doi.org/10.1126/science.abb7015

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