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Coronaviruses

Editor-in-Chief

ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Review Article

Different Variants of SARS-CoV-2: A Comprehensive Review on Mutation Patterns and Pathogenicity

Author(s): Fahmina Rizvi, Mohsin Ali Khan, Waseem Ahmad Ansari, Kajim Ali, Mohd. Aamish Khan and Mohammad Faheem Khan*

Volume 4, Issue 1, 2023

Published on: 17 April, 2023

Article ID: e280323215081 Pages: 11

DOI: 10.2174/2666796704666230328171636

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a single-stranded and positive- sense RNA virus, is exhibiting a great degree of mutation acclimated to variable environments, posing a great threat to human life, with numerous SARS-CoV-2 variants. This review aims to analyze emerging strains of SARS-CoV-2, their mutational pattern, their impact on viral pathogenicity, and the identification of the targets for the development of vaccines and therapeutics against the virus. SARSCoV- 2 consists of four structural protein codes viz, peplomer protein (S), an envelope protein (E), nucleoprotein capsid (N), and matrix protein (M), that are involved in the ingression of the viral genome into the host cell by interacting with the host cell receptor, i.e., human angiotensin-converting enzyme 2 (ACE2) (only S protein is shown to bind to ACE-2 receptor). The review includes consequences of mutations- D614G (pre-dominant mutation), E484K, N501Y, K417N, L452R, P681H, del69/70, del157/158, Ins214EPE, and so forth, in alpha, beta, gamma, delta, omicron including other strains of SARS-CoV-2. Mutations include substitution, deletion, and insertion of amino acids in the spike glycoprotein of the SARS-CoV-2, resulting in antibody neutralization, immune escape, etc. As a consequence of modifications in the nucleotide sequence of the viral genome code pushed on by exposure to various environments, these new strains influence the pathogenicity of the virus.

Keywords: SARS-CoV-2 spike mutations, D614G, N501Y, E484K, amino-acid substitution, RBD-hACE2 interactions.

Graphical Abstract
[1]
Kumar, A.; Ansari, W.A.; Ahamad, T.; Saquib, M.; Khan, M.F. Safe use of Sodium Dodecyl Sulfate (SDS) to deactivate SARS-CoV-2: An evidence-based systematic review. Coronaviruses, 2021, 2(9), e120821189929.
[http://dx.doi.org/10.2174/2666796701666210105114804]
[2]
Shariare, M.H.; Parvez, M.A.K.; Karikas, G.A.; Kazi, M. The growing complexity of COVID-19 drug and vaccine candidates: challenges and critical transitions. J. Infect. Public Health, 2021, 14(2), 214-220.
[http://dx.doi.org/10.1016/j.jiph.2020.12.009] [PMID: 33493917]
[3]
Astuti, I. Ysrafil. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab. Syndr., 2020, 14(4), 407-412.
[http://dx.doi.org/10.1016/j.dsx.2020.04.020] [PMID: 32335367]
[4]
Altincekic, N.; Korn, S.M.; Qureshi, N.S. Large-scale recombinant production of the SARS-CoV-2 proteome for high-throughput and structural biology applications. Front. Mol. Biosci., 2021, 8, 653148.
[http://dx.doi.org/10.3389/fmolb.2021.653148] [PMID: 34041264]
[5]
Qamar, T.M.; Alqahtani, S.M. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J. Pharm. Anal., 2020, 10(4), 313-319.
[http://dx.doi.org/10.1016/j.jpha.2020.03.009]
[6]
Nguyen, H.L.; Lan, P.D.; Thai, N.Q.; Nissley, D.A.; O’Brien, E.P.; Li, M.S. Does SARS-CoV-2 bind to human ACE2 more strongly than does SARS-CoV? J. Phys. Chem. B, 2020, 124(34), 7336-7347.
[http://dx.doi.org/10.1021/acs.jpcb.0c04511] [PMID: 32790406]
[7]
Lu, J.; Sun, P.D. High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity. J. Biol. Chem., 2020, 295(52), 18579-18588.
[http://dx.doi.org/10.1074/jbc.RA120.015303] [PMID: 33122196]
[8]
Lan, J.; Ge, J.; Yu, J. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 2020, 581(7807), 215-220.
[http://dx.doi.org/10.1038/s41586-020-2180-5] [PMID: 32225176]
[9]
Jackson, C.B.; Farzan, M.; Chen, B.; Choe, H. Mechanisms of SARS-CoV-2 entry into cells. Nat. Rev. Mol. Cell Biol., 2022, 23(1), 3-20.
[http://dx.doi.org/10.1038/s41580-021-00418-x] [PMID: 34611326]
[10]
Jaimes, J.A.; Millet, J.K.; Whittaker, G.R. Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 Site. iScience, 2020, 23(6), 101212.
[http://dx.doi.org/10.1016/j.isci.2020.101212] [PMID: 32512386]
[11]
Khan, M.F.; Khan, M.A.; Khan, Z.A.; Ahamad, T.; Ansari, W.A. In silico study to identify dietary molecules as potential SARS-CoV-2 agents. Lett. Drug Des. Discov., 2021, 18(6), 562-573.
[http://dx.doi.org/10.2174/1570180817999201209204153]
[12]
Chen, J.; Wang, R.; Wang, M.; Wei, G.W. Mutations strengthened SARS-CoV-2 infectivity. J. Mol. Biol., 2020, 432(19), 5212-5226.
[http://dx.doi.org/10.1016/j.jmb.2020.07.009] [PMID: 32710986]
[13]
Groves, D.C.; Rowland-Jones, S.L.; Angyal, A. The D614G mutations in the SARS-CoV-2 spike protein: Implications for viral infectivity, disease severity and vaccine design. Biochem. Biophys. Res. Commun., 2021, 538, 104-107.
[http://dx.doi.org/10.1016/j.bbrc.2020.10.109] [PMID: 33199022]
[14]
Thakur, S.; Sasi, S.; Pillai, S.G. SARS-CoV-2 mutations and their impact on diagnostics, therapeutics and vaccines. Front. Med., 2022, 9(9), 815389.
[http://dx.doi.org/10.3389/fmed.2022.815389] [PMID: 35273977]
[15]
Korber, B.; Fischer, W.M.; Gnanakaran, S. Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus. Cell, 2020, 182(4), 812-827.e19.
[http://dx.doi.org/10.1016/j.cell.2020.06.043] [PMID: 32697968]
[16]
Kirby, T. New variant of SARS-CoV-2 in UK causes surge of COVID-19. Lancet Respir. Med., 2021, 9(2), e20-e21.
[http://dx.doi.org/10.1016/S2213-2600(21)00005-9] [PMID: 33417829]
[17]
Davies, N.G.; Abbott, S.; Barnard, R.C. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science, 2021, 372(6538), eabg3055.
[http://dx.doi.org/10.1126/science.abg3055] [PMID: 33658326]
[18]
Weisblum, Y.; Schmidt, F.; Zhang, F. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife, 2020, 9, e61312.
[http://dx.doi.org/10.7554/eLife.61312] [PMID: 33112236]
[19]
Tegally, H.; Wilkinson, E.; Giovanetti, M. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature, 2021, 592(7854), 438-443.
[http://dx.doi.org/10.1038/s41586-021-03402-9] [PMID: 33690265]
[20]
Toovey, O.T.R.; Harvey, K.N.; Bird, P.W.; Tang, J.W.T.W.T. Introduction of Brazilian SARS-CoV-2 484K.V2 related variants into the UK. J. Infect., 2021, 82(5), e23-e24.
[http://dx.doi.org/10.1016/j.jinf.2021.01.025] [PMID: 33548358]
[21]
Planas, D.; Veyer, D.; Baidaliuk, A. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature, 2021, 596(7871), 276-280.
[http://dx.doi.org/10.1038/s41586-021-03777-9] [PMID: 34237773]
[22]
McCallum, M.; Bassi, J.; De Marco, A. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science, 2021, 373(6555), 648-654.
[http://dx.doi.org/10.1126/science.abi7994] [PMID: 34210893]
[23]
West, A.P., Jr; Wertheim, J.O.; Wang, J.C. Detection and characterization of the SARS-CoV-2 lineage B.1.526 in New York. Nat. Commun., 2021, 12(1), 4886.
[http://dx.doi.org/10.1038/s41467-021-25168-4] [PMID: 34373458]
[24]
Bian, L.; Gao, Q.; Gao, F. Impact of the Delta variant on vaccine efficacy and response strategies. Expert Rev. Vaccines, 2021, 20(10), 1201-1209.
[http://dx.doi.org/10.1080/14760584.2021.1976153] [PMID: 34488546]
[25]
Chakraborty, S.; Mallajosyula, V.; Tato, C.M.; Tan, G.S.; Wang, T.T. SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand? Adv. Drug Deliv. Rev., 2021, 172, 314-338.
[http://dx.doi.org/10.1016/j.addr.2021.01.014] [PMID: 33482248]
[26]
Mohammadi, M.; Shayestehpour, M.; Mirzaei, H. The impact of spike mutated variants of SARS-CoV-2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines. Braz. J. Infect. Dis., 2021, 25(4), 101606.
[http://dx.doi.org/10.1016/j.bjid.2021.101606] [PMID: 34428473]
[27]
Hirabara, S.M.; Serdan, T.D.A.; Gorjao, R. SARS-CoV-2 Variants: Differences and potential of immune evasion. Front. Cell. Infect. Microbiol., 2022, 11, 781429.
[http://dx.doi.org/10.3389/fcimb.2021.781429] [PMID: 35118007]
[28]
Lubinski, B.; Fernandes, M.H.V.; Frazier, L. Functional evaluation of the P681H mutation on the proteolytic activation of the SARS-CoV-2 variant B.1.1.7 (Alpha) spike. iScience, 2022, 25(1), 103589.
[http://dx.doi.org/10.1016/j.isci.2021.103589] [PMID: 34909610]
[29]
Plante, J.A.; Liu, Y.; Liu, J. Spike mutation D614G alters SARS-CoV-2 fitness. Nature, 2021, 592(7852), 116-121.
[http://dx.doi.org/10.1038/s41586-020-2895-3] [PMID: 33106671]
[30]
Benton, D.J.; Wrobel, A.G.; Roustan, C. The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2. Proc. Natl. Acad. Sci., 2021, 118(9), e2022586118.
[http://dx.doi.org/10.1073/pnas.2022586118] [PMID: 33579792]
[31]
Yang, T.J.; Yu, P.Y.; Chang, Y.C. Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function. Nat. Struct. Mol. Biol., 2021, 28(9), 731-739.
[http://dx.doi.org/10.1038/s41594-021-00652-z] [PMID: 34385690]
[32]
Galloway, S.E.; Paul, P.; MacCannell, D.R. Emergence of SARS-CoV-2 B.1.1.7 Lineage - United States, December 29, 2020-January 12, 2021. MMWR Morb. Mortal. Wkly. Rep., 2021, 70(3), 95-99.
[http://dx.doi.org/10.15585/mmwr.mm7003e2] [PMID: 33476315]
[33]
Calistri, P.; Amato, L.; Puglia, I. Infection sustained by lineage B.1.1.7 of SARS-CoV-2 is characterised by longer persistence and higher viral RNA loads in nasopharyngeal swabs. Int. J. Infect. Dis., 2021, 105, 753-755.
[http://dx.doi.org/10.1016/j.ijid.2021.03.005] [PMID: 33684558]
[34]
Ramanathan, M.; Ferguson, I.D.; Miao, W.; Khavari, P.A. SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. Lancet Infect. Dis., 2021, 21(8), 1070.
[http://dx.doi.org/10.1016/S1473-3099(21)00262-0] [PMID: 34022142]
[35]
Harvey, W.T.; Carabelli, A.M.; Jackson, B. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol., 2021, 19(7), 409-424.
[http://dx.doi.org/10.1038/s41579-021-00573-0] [PMID: 34075212]
[36]
Baj, A.; Novazzi, F.; Pasciuta, R. Breakthrough infections of E484K-Harboring SARS-CoV-2 delta variant, Lombardy, Italy. Emerg. Infect. Dis., 2021, 27(12), 3180-3182.
[http://dx.doi.org/10.3201/eid2712.211792] [PMID: 34499599]
[37]
Chakraborty, S. E484K and N501Y SARS-CoV-2 spike mutants Increase ACE2 recognition but reduce affinity for neutralizing antibody. Int. Immunopharmacol., 2022, 102, 108424.
[http://dx.doi.org/10.1016/j.intimp.2021.108424] [PMID: 34915409]
[38]
Wang, P.; Nair, M.S.; Liu, L. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature, 2021, 593(7857), 130-135.
[http://dx.doi.org/10.1038/s41586-021-03398-2] [PMID: 33684923]
[39]
Sanches, P.R.S.; Charlie-Silva, I.; Braz, H.L.B. Recent advances in SARS-CoV-2 Spike protein and RBD mutations comparison between new variants Alpha (B.1.1.7, United Kingdom), Beta (B.1.351, South Africa), Gamma (P.1, Brazil) and Delta (B.1.617.2, India). J. Virus Erad., 2021, 7(3), 100054.
[http://dx.doi.org/10.1016/j.jve.2021.100054] [PMID: 34548928]
[40]
Barton, M.I.; MacGowan, S.A.; Kutuzov, M.A.; Dushek, O.; Barton, G.J.; van der Merwe, P.A. Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics. eLife, 2021, 10, e70658.
[http://dx.doi.org/10.7554/eLife.70658] [PMID: 34435953]
[41]
Chen, C.; Boorla, V.S.; Banerjee, D. Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike RBD and human ACE2. Proc. Natl. Acad. Sci., 2021, 118(42), e2106480118.
[http://dx.doi.org/10.1073/pnas.2106480118] [PMID: 34588290]
[42]
Gálvez, J.M.; Chaparro-Solano, H.M.; Pinzón-Rondón, Á.M. Mutation profile of SARS-CoV-2 genome in a sample from the first year of the pandemic in Colombia. Infect. Genet. Evol., 2022, 97, 105192.
[http://dx.doi.org/10.1016/j.meegid.2021.105192] [PMID: 34933126]
[43]
Ferreira, I.A.T.M.; Kemp, S.A.; Datir, R. SARS-CoV-2 B.1.617 mutations L452R and E484Q are not synergistic for antibody evasion. J. Infect. Dis., 2021, 224(6), 989-994.
[http://dx.doi.org/10.1093/infdis/jiab368] [PMID: 34260717]
[44]
Shiehzadegan, S.; Alaghemand, N.; Fox, M.; Venketaraman, V. Analysis of the Delta variant B.1.617.2 COVID-19. Clin. Pract., 2021, 11(4), 778-784.
[http://dx.doi.org/10.3390/clinpract11040093] [PMID: 34698149]
[45]
Mlcochova, P.; Kemp, S.A.; Dhar, M.S. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature, 2021, 599(7883), 114-119.
[http://dx.doi.org/10.1038/s41586-021-03944-y] [PMID: 34488225]
[46]
Cherian, S.; Potdar, V.; Jadhav, S. SARS-CoV-2 spike mutations, L452R, T478K, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India. Microorganisms, 2021, 9(7), 1542.
[http://dx.doi.org/10.3390/microorganisms9071542] [PMID: 34361977]
[47]
Martínez-Flores, D.; Zepeda-Cervantes, J.; Cruz-Reséndiz, A.; Aguirre-Sampieri, S.; Sampieri, A.; Vaca, L. SARS-CoV-2 Vaccines based on the spike glycoprotein and implications of new viral variants. Front. Immunol., 2021, 12, 701501.
[http://dx.doi.org/10.3389/fimmu.2021.701501] [PMID: 34322129]
[48]
Aleem, A.; Akbar Samad, A.B.; Slenker, A.K. Emerging variants of SARS-CoV-2 and novel therapeutics against Coronavirus (COVID-19). Treasure Island (FL); Florida, US: StatPearls Publishing, 2022.
[49]
Salehi-Vaziri, M.; Fazlalipour, M.; Seyed Khorrami, S.M. The ins and outs of SARS-CoV-2 variants of concern (VOCs). Arch. Virol., 2022, 167(2), 327-344.
[http://dx.doi.org/10.1007/s00705-022-05365-2] [PMID: 35089389]
[50]
Rose, R.; Nolan, D.J.; LaFleur, T.M.; Lamers, S.L. Outbreak of P.3 (Theta) SARS-CoV-2 emerging variant of concern among service workers in Louisiana. J. Infect. Public Health, 2022, 15(1), 7-9.
[http://dx.doi.org/10.1016/j.jiph.2021.11.011] [PMID: 34856435]
[51]
Tools to explore COVID-19 and SARS-CoV-2 data with variant surveillance reports, data on cases and deaths, and a standardized, searchable research library. Available from: https://outbreak.info
[52]
Zhou, H.; Dcosta, B.M.; Samanovic, M.I.; Mulligan, M.J.; Landau, N.R.; Tada, T.B. 1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies. MBio, 2021, 12(4), e01386-e21.
[http://dx.doi.org/10.1128/mBio.01386-21] [PMID: 34311587]
[53]
Giron, C.C.; Laaksonen, A.; Barroso da Silva, F.L. Up state of the SARS-CoV-2 spike homotrimer favors an increased virulence for new variants. Frontiers in Medical Technology, 2021, 3, 694347.
[http://dx.doi.org/10.3389/fmedt.2021.694347] [PMID: 35047936]
[54]
Wink, P.L.; Volpato, F.C.Z.; Monteiro, F.L. First identification of SARS-CoV-2 Lambda (C.37) variant in Southern Brazil. Infect. Control Hosp. Epidemiol., 2021, 2021, 1-2.
[http://dx.doi.org/10.1017/ice.2021.390] [PMID: 34470685]
[55]
Darvishi, M.; Rahimi, F.; Abadi, T.B.A. SARS-CoV-2 Lambda (C.37): An emerging variant of concern? Gene Rep., 2021, 25, 101378.
[http://dx.doi.org/10.1016/j.genrep.2021.101378] [PMID: 34632160]
[57]
Tada, T.; Zhou, H.; Dcosta, B.M. High-titer neutralization of Mu and C.1.2 SARS-CoV-2 variants by vaccine-elicited antibodies of previously infected individuals. Cell Rep., 2022, 38(2), 110237.
[http://dx.doi.org/10.1016/j.celrep.2021.110237] [PMID: 34982967]
[58]
Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. Available from: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern
[59]
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., 2022, 94(4), 1255-1256.
[http://dx.doi.org/10.1002/jmv.27491] [PMID: 34850421]
[60]
VanBlargan, L.A.; Errico, J.M.; Halfmann, P.J. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat. Med., 2022, 28(3), 490-495.
[http://dx.doi.org/10.1038/s41591-021-01678-y] [PMID: 35046573]
[61]
Kannan, S.; Ali, S.S.P.; Sheeza, A. Omicron (B.1.1.529)-variant of concern-molecular profile and epidemiology: A mini review. Eur. Rev. Med. Pharmacol. Sci., 2021, 25(24), 8019-8022.
[http://dx.doi.org/10.26355/eurrev_202112_27653] [PMID: 34982466]
[62]
Wise, J. COVID-19: The E484K mutation and the risks it poses. BMJ, 2021, 372(359), n359.
[http://dx.doi.org/10.1136/bmj.n359] [PMID: 33547053]
[63]
Saito, A.; Irie, T.; Suzuki, R. Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation. Nature, 2022, 602(7896), 300-306.
[http://dx.doi.org/10.1038/s41586-021-04266-9] [PMID: 34823256]
[64]
Motozono, C.; Toyoda, M.; Zahradnik, J. SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity. Cell Host Microbe, 2021, 29(7), 1124-1136.e11.
[http://dx.doi.org/10.1016/j.chom.2021.06.006] [PMID: 34171266]
[65]
Zhou, W.; Xu, C.; Wang, P. N439K variant in spike protein alter the infection efficiency and antigenicity of SARS-CoV-2 based on molecular dynamics simulation. Front. Cell Dev. Biol., 2021, 9, 697035.
[http://dx.doi.org/10.3389/fcell.2021.697035] [PMID: 34414185]
[66]
Jangra, S.; Ye, C.; Rathnasinghe, R. SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. Lancet Microbe, 2021, 2(7), e283-e284.
[http://dx.doi.org/10.1016/S2666-5247(21)00068-9] [PMID: 33846703]
[67]
Thakur, V.; Ratho, R.K. OMICRON (B.1.1.529): A new SARS‐CoV‐2 variant of concern mounting worldwide fear. J. Med. Virol., 2022, 94(5), 1821-1824.
[http://dx.doi.org/10.1002/jmv.27541] [PMID: 34936120]
[68]
Thomson, E.C.; Rosen, L.E.; Shepherd, J.G. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Cell, 2021, 184(5), 1171-1187.e20.
[http://dx.doi.org/10.1016/j.cell.2021.01.037] [PMID: 33621484]

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