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Distinctive Combinations of RBD Mutations Contribute to Antibody Evasion in the Case of the SARS-CoV-2 Beta Variant

  • Tae-Hun Kim (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University) ;
  • Sojung Bae (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University) ;
  • Sunggeun Goo (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University) ;
  • Jinjong Myoung (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University)
  • Received : 2023.08.14
  • Accepted : 2023.10.13
  • Published : 2023.12.28

Abstract

Since its first report in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a grave threat to public health. Virus-specific countermeasures, such as vaccines and therapeutics, have been developed and have contributed to the control of the viral pandemic, which has become endemic. Nonetheless, new variants continue to emerge and could cause a new pandemic. Consequently, it is important to comprehensively understand viral evolution and the roles of mutations in viral infectivity and transmission. SARS-CoV-2 beta variant encode mutations (D614G, N501Y, E484K, and K417N) in the spike which are frequently found in other variants as well. While their individual role in viral infectivity has been elucidated against various therapeutic antibodies, it still remains unclear whether those mutations may act additively or synergistically when combined. Here, we report that N501Y mutation shows differential effect on two therapeutic antibodies tested. Interestingly, the relative importance of E484K and K417N mutations in antibody evasion varies depending on the antibody type. Collectively, these findings suggest that continuous efforts to develop effective antibody therapeutics and combinatorial treatment with multiple antibodies are more rational and effective forms of treatment.

Keywords

Acknowledgement

The research was performed with the support by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2021M3E5E3080533). And we thank Dr. Kyu-Jin Park and Dr. Yeon-Sook Kim for their generous gifts of the antibodies used in this study.

References

  1. Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J, et al. 2021. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592: 438-443.
  2. Kim EH, Kim YI, Jang SG, Im M, Jeong K, Choi YK, et al. 2021. Antiviral effects of human placenta hydrolysate (Laennec((R))) against SARS-CoV-2 in vitro and in the ferret model. J. Microbiol. 59: 1056-1062.
  3. Kim C, Kim JD, Seo SU. 2022. Nanoparticle and virus-like particle vaccine approaches against SARS-CoV-2. J. Microbiol. 60: 335-346.
  4. Kim YI, Casel MAB, Choi YK. 2022. Transmissibility and pathogenicity of SARS-CoV-2 variants in animal models. J. Microbiol. 60: 255-267.
  5. Lee MH, Kim BJ. 2022. COVID-19 vaccine development based on recombinant viral and bacterial vector systems: combinatorial effect of adaptive and trained immunity. J. Microbiol. 60: 321-334.
  6. Mattoo SU, Myoung J. 2022. T cell responses to SARS-CoV-2 in humans and animals. J. Microbiol. 60: 276-289.
  7. Myoung J. 2022. Two years of COVID-19 pandemic: where are we now? J. Microbiol. 60: 235-237.
  8. Park U, Cho NH. 2022. Protective and pathogenic role of humoral responses in COVID-19. J. Microbiol. 60: 268-275.
  9. Lee HJ, Choi H, Nowakowska A, Kang LW, Kim M, Kim YB. 2023. Antiviral activity against SARS-CoV-2 variants using in silico and in vitro approaches. J. Microbiol. 61: 703-711.
  10. Ku KB, Shin HJ, Kim HS, Kim BT, Kim SJ, Kim C. 2020. Repurposing screens of FDA-approved drugs identify 29 inhibitors of SARS-CoV-2. J. Microbiol. Biotechnol. 30: 1843-1853.
  11. Mattoo SS, Myoung J. 2021. A promising vaccination strategy against COVID-19 on the horizon: Heterologous immunization. J. Microbiol Biotechnol. 31: 1601-1614.
  12. Zhou YF, Nie JJ, Shi C, Ning K, Cao YF, Xie Y, et al. 2022. Expression and immunogenicity of SARS-CoV-2 virus-like particles based on recombinant truncated HEV-3 ORF2 capsid protein. J. Microbiol. Biotechnol. 32: 1335-1343.
  13. Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B, et al. 2006. Discovery of an RNA virus 3?→5? exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc. Natl. Acad. Sci. USA 103: 5108-5113.
  14. Eckerle LD, Becker MM, Halpin RA, Li K, Venter E, Lu X, et al. 2010. Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing. PLoS Pathog. 6: e1000896.
  15. Tao K, Tzou PL, Nouhin J, Gupta RK, De Oliveira T, Kosakovsky Pond SL, et al. 2021. The biological and clinical significance of emerging SARS-CoV-2 variants. Nature Rev. Genet. 22: 757-773.
  16. Jeong HW, Chang HH, Kim EJ, Kim YK, Kim SM, Kim EH, et al. 2021. Differences in seroprevalence between epicenter and non-epicenter areas of the COVID-19 outbreak in South Korea. J. Microbiol. 59: 530-533.
  17. Na W, Moon H, Song D. 2021. A comprehensive review of SARS-CoV-2 genetic mutations and lessons from animal coronavirus recombination in one health perspective. J. Microbiol. 59: 332-340.
  18. Soh SM, Kim Y, Kim C, Jang US, Lee HR. 2021. The rapid adaptation of SARS-CoV-2-rise of the variants: transmission and resistance. J. Microbiol. 59: 807-818.
  19. Chemaitelly H, Bertollini R, Abu-Raddad LJ. 2021. Efficacy of natural immunity against SARS-CoV-2 reinfection with the beta variant. New Engl. J. Med. 385: 2585-2586.
  20. Riou C, Keeton R, Moyo-Gwete T, Hermanus T, Kgagudi P, Baguma R, et al. 2022. Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity. Sci. Transl. Med. 14: eabj6824.
  21. Zhang J, Cai Y, Xiao T, Lu J, Peng H, Sterling SM, et al. 2021. Structural impact on SARS-CoV-2 spike protein by D614G substitution. Science 372: 525-530.
  22. Li Q, Wu J, Nie J, Zhang L, Hao H, Liu S, et al. 2020. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 182: 1284-1294 e1289.
  23. Motozono C, Toyoda M, Zahradnik J, Saito A, Nasser H, Tan TS, et al. 2021. SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity. Cell Host Microbe. 29: 1124-1136 e1111.
  24. Khan A, Zia T, Suleman M, Khan T, Ali SS, Abbasi AA, et al. 2021. Higher infectivity of the SARS-CoV-2 new variants is associated with K417N/T, E484K, and N501Y mutants: An insight from structural data. J. Cell. Physiol. 236: 7045-7057.
  25. Jeong JY, Yim HS, Ryu JY, Lee HS, Lee JH, Seen DS, et al. 2012. One-step sequence- and ligation-independent cloning as a rapid and versatile cloning method for functional genomics studies. Appl. Environ. Microbiol. 78: 5440-5443.
  26. Islam MN, Lee KW, Yim HS, Lee SH, Jung HC, Lee JH, et al. 2017. Optimizing T4 DNA polymerase conditions enhances the efficiency of one-step sequence- and ligation-independent cloning. Biotechniques 63: 125-130.
  27. Bae S, Lee JY, Myoung J. 2020. Chikungunya virus nsP2 Impairs MDA5/RIG-I-mediated induction of NF-kappaB promoter activation: A potential target for virus-specific therapeutics. J. Microbiol. Biotechnol. 30: 1801-1809.
  28. Lee JY, Nguyen TTN, Myoung J. 2020. Zika virus-encoded NS2A and NS4A strongly downregulate NF-kappaB promoter activity. J. Microbiol. Biotechnol. 30: 1651-1658.
  29. Lee HJ, Park M, Choi H, Nowakowska A, Moon C, Kwak JH, et al. 2021. Pine needle extract applicable to topical treatment for the prevention of human papillomavirus infection. J. Microbiol. Biotechnol. 31: 137-143.
  30. Kim S. 2022. COVID-19 drug development. J. Microbiol. Biotechnol. 32: 1-5.
  31. Lee SJ, Kim YJ, Ahn DG. 2022. Distinct molecular mechanisms characterizing pathogenesis of SARS-CoV-2. J. Microbiol. Biotechnol. 32: 1073-1085.
  32. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. 2020. Structure, dunction, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 183: 1735.
  33. Letko M, Marzi A, Munster V. 2020. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 5: 562-569.
  34. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181: 271-280 e278.
  35. Wrobel AG, Benton DJ, Roustan C, Borg A, Hussain S, Martin SR, et al. 2022. Evolution of the SARS-CoV-2 spike protein in the human host. Nat. Commun. 13: 1178.
  36. Weissman D, Alameh MG, de Silva T, Collini P, Hornsby H, Brown R, et al. 2021. D614G Spike mutation increases SARS CoV-2 susceptibility to neutralization. Cell Host Microbe. 29: 23-31 e24.
  37. Kim YJ, Jang US, Soh SM, Lee JY, Lee HR. 2021. The impact on infectivity and neutralization efficiency of SARS-CoV-2 lineage B.1.351 pseudovirus. Viruses 13: 633.
  38. Cele S, Gazy I, Jackson L, Hwa S-H, Tegally H, Lustig G, et al. 2021. Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature 593: 142-146.
  39. Salleh MZ, Derrick JP, Deris ZZ. 2021. Structural evaluation of the spike glycoprotein variants on SARS-CoV-2 transmission and immune evasion. Int. J. Mol. Sci. 22: 7425.
  40. Tao K, Tzou PL, Nouhin J, Gupta RK, de Oliveira T, Kosakovsky Pond SL, et al. 2021. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat. Rev. Genet. 22: 757-773.
  41. Baum A, Kyratsous CA. 2021. SARS-CoV-2 spike therapeutic antibodies in the age of variants. J. Exp. Med. 218: e20210198.
  42. Starr TN, Greaney AJ, Hilton SK, Ellis D, Crawford KHD, Dingens AS, et al. 2020. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 182: 1295-1310 e1220.
  43. Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, et al. 2021. Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature 593: 266-269.