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Engineered Therapeutic Antibody Against SARS-CoV-2

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Abstract

Purpose of Review

The success and failure of therapeutic antibodies against SARS-CoV-2 offer a lesson on therapeutic antibody design and development.

Recent Findings

Therapeutic antibody against SARS-CoV-2 facing challenging antibody escape mutation. A paratope design strategy targeting pancoronavirus conserved epitope(s) and combining two antibodies as antibody cocktails or bispecific antibodies may overcome antibody escape mutations of the SARS-CoV-2 spike. Instead of designing broadly neutralizing antibodies, repurposing antibodies can target viral or host molecules to inhibit the virus and alleviate dysregulation of the host immune response.

Summary

Detailed strategies for engineering therapeutic antibodies, including antibody format, are reviewed in this article.

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Data Availability

No datasets were generated or analyzed during the current study.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Holmes EC, Goldstein SA, Rasmussen AL, Robertson DL, Crits-Christoph A, Wertheim JO, et al. The origins of SARS-CoV-2: a critical review. Cell. 2021;184(19):4848–56. https://doi.org/10.1016/j.cell.2021.08.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen J. Pathogenicity and transmissibility of 2019-nCoV-A quick overview and comparison with other emerging viruses. Microbes Infect. 2020;22(2):69–71. https://doi.org/10.1016/j.micinf.2020.01.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. WHO. WHO Coronavirus (COVID-19) dashboard. 2023. https://covid19.who.int/ (accessed 2023, July 28).

  4. WHO. Statement on the fourteenth meeting of the International Health Regulations (2023, Jan 30). 2023. https://www.who.int/news/ (accessed 2023, July 28).

  5. WHO. Statement on the fourteenth meeting of the International Health Regulations (2023, May 5). 2023 https://www.who.int/news/ (accessed 2023, July 28).

  6. Al-Kuraishy HM, Al-Fakhrany OM, Elekhnawy E, Al-Gareeb AI, Alorabi M, De Waard M, et al. Traditional herbs against COVID-19: back to old weapons to combat the new pandemic. Eur J Med Res. 2022;27(1):186. https://doi.org/10.1186/s40001-022-00818-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hwang YC, Lu RM, Su SC, Chiang PY, Ko SH, Ke FY, et al. Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection. J Biomed Sci. 2022;29(1):1. https://doi.org/10.1186/s12929-021-00784-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lei S, Chen X, Wu J, Duan X, Men K. Small molecules in the treatment of COVID-19. Signal Transduct Target Ther. 2022;7(1):387. https://doi.org/10.1038/s41392-022-01249-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Puhl AC, Lane TR, Urbina F, Ekins S. The need for speed and efficiency: a brief review of small molecule antivirals for COVID-19. Front Drug Discov. 2022;2:837587. https://doi.org/10.3389/fddsv.2022.837587.

    Article  Google Scholar 

  10. Zhong L, Zhao Z, Peng X, Zou J, Yang S. Recent advances in small-molecular therapeutics for COVID-19. Precis Clin Med. 2022;5(4):pbac024. https://doi.org/10.1093/pcmedi/pbac024.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yang J, Won G, Baek JY, Lee YH, Kim H, Huh K, et al. Neutralizing activity against Omicron BA.5 after tixagevimab/cilgavimab administration comparable to those after Omicron BA.1/BA.2 breakthrough infections. Front Immunol. 2023;14:1139980. https://doi.org/10.3389/fimmu.2023.1139980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jakimovski D, Eckert SP, Mirmosayyeb O, Thapa S, Pennington P, Hojnacki D, et al. Tixagevimab and cilgavimab (Evusheld™) prophylaxis prevents breakthrough COVID-19 infections in immunosuppressed population: 6-month prospective study. Vaccines (Basel). 2023;11(2):350. https://doi.org/10.3390/vaccines11020350.

    Article  CAS  PubMed  Google Scholar 

  13. Kauer V, Totschnig D, Waldenberger F, Augustin M, Karolyi M, Nägeli M, et al. Efficacy of sotrovimab (SOT), molnupiravir (MOL), and nirmatrelvir/ritponavir (N/R) and tolerability of molnupiravir in outpatients at high risk for severe COVID-19. Viruses. 2023;15(5):1181. https://doi.org/10.3390/v15051181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brant AC, Tian W, Majerciak V, Yang W, Zheng ZM. SARS-CoV-2: from its discovery to genome structure, transcription, and replication. Cell Biosci. 2021;11(1):136. https://doi.org/10.1186/s13578-021-00643-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rodriguez-Morales AJ, Bonilla-Aldana DK, Balbin-Ramon GJ, Rabaan AA, Sah R, Paniz-Mondolfi A, et al. History is repeating itself: probable zoonotic spillover as the cause of the 2019 novel Coronavirus Epidemic. Infez Med. 2020;28(1):3–5.

    CAS  PubMed  Google Scholar 

  16. Haider N, Rothman-Ostrow P, Osman AY, Arruda LB, Macfarlane-Berry L, Elton L, et al. COVID-19-zoonosis or emerging infectious disease? Front Public Health. 2020;8:596944. https://doi.org/10.3389/fpubh.2020.596944.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhu Z, Lian X, Su X, Wu W, Marraro GA, Zeng Y. From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir Res. 2020;21(1):224. https://doi.org/10.1186/s12931-020-01479-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pustake M, Tambolkar I, Giri P, Gandhi C. SARS, MERS and CoVID-19: an overview and comparison of clinical, laboratory and radiological features. J Family Med Prim Care. 2022;11(1):10–7. https://doi.org/10.4103/jfmpc.jfmpc_839_21.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wang L, Møhlenberg M, Wang P, Zhou H. Immune evasion of neutralizing antibodies by SARS-CoV-2 Omicron. Cytokine Growth Factor Rev. 2023;70:13–25. https://doi.org/10.1016/j.cytogfr.2023.03.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yan W, Zheng Y, Zeng X, He B, Cheng W. Structural biology of SARS-CoV-2: open the door for novel therapies. Signal Transduct Target Ther. 2022;7(1):26. https://doi.org/10.1038/s41392-022-00884-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41(9):1141–9. https://doi.org/10.1038/s41401-020-0485-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu XH, Cheng T, Liu BY, Chi J, Shu T, Wang T. Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development. Front Pharmacol. 2022;13:955648. https://doi.org/10.3389/fphar.2022.955648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhou Y, Lu X, Wang X, Ying T, Tan X. Potent therapeutic strategies for COVID-19 with single-domain antibody immunoliposomes neutralizing SARS-CoV-2 and Lip/cGAMP enhancing protective immunity. Int J Mol Sci. 2023;24(4):4068. https://doi.org/10.3390/ijms24044068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. VanBlargan LA, Errico JM, Halfmann PJ, Zost SJ, Crowe JE Jr, Purcell LA, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med. 2022;28(3):490–5. https://doi.org/10.1038/s41591-021-01678-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang L, Jackson CB, Mou H, Ojha A, Peng H, Quinlan BD, et al. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat Commun. 2020;11(1):6013. https://doi.org/10.1038/s41467-020-19808-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. 2022;23(1):3–20. https://doi.org/10.1038/s41580-021-00418-x.

    Article  CAS  PubMed  Google Scholar 

  27. Tuccori M, Ferraro S, Convertino I, Cappello E, Valdiserra G, Blandizzi C, et al. Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline. MAbs. 2020;12(1):1854149. https://doi.org/10.1080/19420862.2020.1854149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Miljanovic D, Cirkovic A, Lazarevic I, Knezevic A, Cupic M, Banko A. Clinical efficacy of anti-SARS-CoV-2 monoclonal antibodies in preventing hospitalisation and mortality among patients infected with Omicron variants: a systematic review and meta-analysis. Rev Med Virol. 2023;33(4):e2439. https://doi.org/10.1002/rmv.2439.

    Article  CAS  PubMed  Google Scholar 

  29. McCallum M, De Marco A, Lempp FA, Tortorici MA, Pinto D, Walls AC, et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell. 2021;184(9):2332-2347.e16. https://doi.org/10.1016/j.cell.2021.03.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hastie KM, Li H, Bedinger D, Schendel SL, Dennison SM, Li K, et al. Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: a global consortium study. Science. 2021;374(6566):472–8. https://doi.org/10.1126/science.abh2315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Suryadevara N, Shrihari S, Gilchuk P, VanBlargan LA, Binshtein E, Zost SJ, et al. Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell. 2021;184(9):2316-2331.e15. https://doi.org/10.1016/j.cell.2021.03.029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Westendorf K, Žentelis S, Wang L, Foster D, Vaillancourt P, Wiggin M, et al. LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. Cell Rep. 2022;39(7):110812. https://doi.org/10.1016/j.celrep.2022.110812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhang H, Lv P, Jiang J, Liu Y, Yan R, Shu S, et al. Advances in developing ACE2 derivatives against SARS-CoV-2. Lancet Microbe. 2023;4(5):e369–78. https://doi.org/10.1016/S2666-5247(23)00011-3.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Xu J, Xu K, Jung S, Conte A, Lieberman J, Muecksch F, et al. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. Nature. 2021;595(7866):278–82. https://doi.org/10.1038/s41586-021-03676-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bertoglio F, Fühner V, Ruschig M, Heine PA, Abassi L, Klünemann T, et al. A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations. Cell Rep. 2021;36(4):109433. https://doi.org/10.1016/j.celrep.2021.109433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shi Z, Li X, Wang L, Sun Z, Zhang H, Chen X, et al. Structural basis of nanobodies neutralizing SARS-CoV-2 variants. Structure. 2022;30(5):707-720.e5. https://doi.org/10.1016/j.str.2022.02.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wang W, Hu Y, Li B, Wang H, Shen J. Applications of nanobodies in the prevention, detection, and treatment of the evolving SARS-CoV-2. Biochem Pharmacol. 2023;208:115401. https://doi.org/10.1016/j.bcp.2022.115401.

    Article  CAS  PubMed  Google Scholar 

  38. •• Starr TN, Czudnochowski N, Liu Z, Zatta F, Park YJ, Addetia A, et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature. 2021;597(7874):97–102. https://doi.org/10.1038/s41586-021-03807-6. (The antibody that interacted with spike protein across subgenus Sarbecoviruses demonstrated cross-variant SARS-CoV-2 protection.)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wrapp D, De Vlieger D, Corbett KS, Torres GM, Wang N, Van Breedam W, et al. Structural basis for potent neutralization of betacoronaviruses by single-domain camelid antibodies. Cell. 2020;181(5):1004-1015.e15. https://doi.org/10.1016/j.cell.2020.04.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tortorici MA, Beltramello M, Lempp FA, Pinto D, Dang HV, Rosen LE, et al. Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. Science. 2020;370(6519):950–7. https://doi.org/10.1126/science.abe3354.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Xiang Y, Nambulli S, Xiao Z, Liu H, Sang Z, Duprex WP, et al. Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2. Science. 2020;370(6523):1479–84. https://doi.org/10.1126/science.abe4747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chi X, Yan R, Zhang J, Zhang G, Zhang Y, Hao M, et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science. 2020;369(6504):650–5. https://doi.org/10.1126/science.abc6952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Suryadevara N, Shiakolas AR, VanBlargan LA, Binshtein E, Chen RE, Case JB, et al. An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer. J Clin Invest. 2022;132(11):e159062. https://doi.org/10.1172/JCI159062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kan Q, Lin X, Li T, Ke X, Jian X, Hou L, et al. A novel mAb broadly neutralizes SARS-CoV-2 VOCs in vitro and in vivo, including the Omicron variants. J Med Virol. 2023;95(3):e28657. https://doi.org/10.1002/jmv.28657.

    Article  CAS  PubMed  Google Scholar 

  45. Silva RP, Huang Y, Nguyen AW, Hsieh CL, Olaluwoye OS, Kaoud TS, et al. Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses. Elife. 2023;12:e83710. https://doi.org/10.7554/eLife.83710.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ryu DK, Song R, Kim M, Kim YI, Kim C, Kim JI, et al. Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant. Biochem Biophys Res Commun. 2021;566:135–40. https://doi.org/10.1016/j.bbrc.2021.06.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li W, Chen C, Drelich A, Martinez DR, Gralinski LE, Sun Z, et al. Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection. Proc Natl Acad Sci U S A. 2020;117(47):29832–8. https://doi.org/10.1073/pnas.2010197117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Fang Y, Sun P, Xie X, Du M, Du F, Ye J, et al. An antibody that neutralizes SARS-CoV-1 and SARS-CoV-2 by binding to a conserved spike epitope outside the receptor binding motif. Sci Immunol. 2022;7(76):eabp9962. https://doi.org/10.1126/sciimmunol.abp9962.

    Article  PubMed  Google Scholar 

  49. Cameroni E, Bowen JE, Rosen LE, Saliba C, Zepeda SK, Culap K, et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature. 2022;602(7898):664–70. https://doi.org/10.1038/s41586-021-04386-2.

    Article  CAS  PubMed  Google Scholar 

  50. U.S. Food and drug administration. FDA announces Bebtelovimab is not currently authorized in any US region. 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-bebtelovimab-not-currently-authorized-any-us-region (assessed 2023, July 28).

  51. Cathcart AL, Havenar-Daughton C, Lempp FA, Ma D, Schmid MA, Agostini ML. The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. bioRxiv [Preprint] 2021.03.09.434607. https://doi.org/10.1101/2021.03.09.434607

  52. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Cicchitto G, Cardillo L, Sequino D, Sabatini P, Adamo L, Marchitiello R, et al. Effectiveness of sotrovimab in the omicron storm time: a case series. Viruses. 2022;15(1):102. https://doi.org/10.3390/v15010102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cheng MM, Reyes C, Satram S, Birch H, Gibbons DC, Drysdale M, et al. Real-world effectiveness of sotrovimab for the early treatment of COVID-19 during SARS-CoV-2 delta and omicron waves in the USA. Infect Dis Ther. 2023;12(2):607–21. https://doi.org/10.1007/s40121-022-00755-0.

    Article  PubMed  PubMed Central  Google Scholar 

  55. •• Copin R, Baum A, Wloga E, Pascal KE, Giordano S, Fulton BO, et al. The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies. Cell. 2021;184(15):3949-3961.e11. https://doi.org/10.1016/j.cell.2021.06.002. (This study demonstrated the combination of antibodies reduced antibody-escape variants.)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chatterjee S, Bhattacharya M, Dhama K, Lee SS, Chakraborty C. Can the RBD mutation R346X provide an additional fitness to the “variant soup”, including offspring of BQ and XBB of SARS-CoV-2 Omicron for the antibody resistance? Mol Ther Nucleic Acids. 2023;32:61–3. https://doi.org/10.1016/j.omtn.2023.02.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. • Birnie E, Biemond JJ, Appelman B, de Bree GJ, Jonges M, Welkers MRA, et al. Development of resistance-associated mutations after sotrovimab administration in high-risk individuals infected with the SARS-CoV-2 omicron variant. JAMA. 2022;328(11):1104–7. https://doi.org/10.1001/jama.2022.13854. (This study reported an antibody’s pressure led to the antibody-escape mutation (s).)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gliga S, Lübke N, Killer A, Gruell H, Walker A, Dilthey AT, et al. Rapid selection of sotrovimab escape variants in severe acute respiratory syndrome coronavirus 2 omicron-infected immunocompromised patients. Clin Infect Dis. 2023;76(3):408–15. https://doi.org/10.1093/cid/ciac802.

    Article  CAS  PubMed  Google Scholar 

  59. Yadav R, Courouble VV, Dey SK, Harrison JJEK, Timm J, Hopkins JB, et al. Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro. Sci Adv. 2022;8(49):eadd2191. https://doi.org/10.1126/sciadv.add2191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kirchdoerfer RN, Ward AB. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun. 2019;10(1):2342. https://doi.org/10.1038/s41467-019-10280-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Subissi L, Posthuma CC, Collet A, Zevenhoven-Dobbe JC, Gorbalenya AE, Decroly E, et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc Natl Acad Sci U S A. 2014;111(37):E3900–9. https://doi.org/10.1073/pnas.1323705111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Malone B, Urakova N, Snijder EJ, Campbell EA. Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design. Nat Rev Mol Cell Biol. 2022;23(1):21–39. https://doi.org/10.1038/s41580-021-00432-z.

    Article  CAS  PubMed  Google Scholar 

  63. Verba K, Gupta M, Azumaya C, Moritz M, Pourmal S, Diallo A, et al. CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes. Res Sq [Preprint]. 2021;rs.3.rs-515215. https://doi.org/10.21203/rs.3.rs-515215/v1.

  64. Armstrong LA, Lange SM, Dee Cesare V, Matthews SP, Nirujogi RS, Cole I, et al. Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies. PLoS ONE. 2021;16(7):e0253364. https://doi.org/10.1371/journal.pone.0253364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Azizogli AR, Pai V, Coppola F, Jafari R, Dodd-O JB, Harish R, et al. Scalable inhibitors of the Nsp3-Nsp4 coupling in SARS-CoV-2. ACS Omega. 2023;8(6):5349–60. https://doi.org/10.1021/acsomega.2c06384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kandwal S, Fayne D. Genetic conservation across SARS-CoV-2 non-structural proteins - insights into possible targets for treatment of future viral outbreaks. Virology. 2023;581:97–115. https://doi.org/10.1016/j.virol.2023.02.011.

    Article  CAS  PubMed  Google Scholar 

  67. Qiao H, Li L, Wang L, Yu H, Hu F, Zhou X, et al. Preparation and characterization of nanobodies targeting SARS-CoV-2 papain-like protease. Protein Expr Purif. 2023;207:106267. https://doi.org/10.1016/j.pep.2023.106267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;582(7811):289–93. https://doi.org/10.1038/s41586-020-2223-y.

    Article  CAS  PubMed  Google Scholar 

  69. Sun Z, Wang L, Li X, Fan C, Xu J, Shi Z, et al. An extended conformation of SARS-CoV-2 main protease reveals allosteric targets. Proc Natl Acad Sci U S A. 2022;119(15):e2120913119. https://doi.org/10.1073/pnas.2120913119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Glab-Ampai K, Kaewchim K, Saenlom T, Thepsawat W, Mahasongkram K, Sookrung N, et al. Human superantibodies to 3CLpro inhibit replication of SARS-CoV-2 across variants. Int J Mol Sci. 2022;23(12):6587. https://doi.org/10.3390/ijms23126587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pan Y, Chandrashekaran IR, Tennant L, Rossjohn J, Littler DR. Inside-out: antibody-binding reveals potential folding hinge-points within the SARS-CoV-2 replication co-factor nsp9. PLoS ONE. 2023;18(4):e0283194. https://doi.org/10.1371/journal.pone.0283194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Slanina H, Madhugiri R, Bylapudi G, Schultheiß K, Karl N, Gulyaeva A, et al. Coronavirus replication-transcription complex: vital and selective NMPylation of a conserved site in nsp9 by the NiRAN-RdRp subunit. Proc Natl Acad Sci U S A. 2021;118(6):e2022310118. https://doi.org/10.1073/pnas.2022310118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Miknis ZJ, Donaldson EF, Umland TC, Rimmer RA, Baric RS, Schultz LW. Severe acute respiratory syndrome coronavirus nsp9 dimerization is essential for efficient viral growth. J Virol. 2009;83(7):3007–18. https://doi.org/10.1128/JVI.01505-08.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Esposito G, Hunashal Y, Percipalle M, Venit T, Dieng MM, Fogolari F, et al. NMR-based analysis of nanobodies to SARS-CoV-2 Nsp9 reveals a possible antiviral strategy against COVID-19. Adv Biol (Weinh). 2021;5(12):e2101113. https://doi.org/10.1002/adbi.202101113.

    Article  CAS  PubMed  Google Scholar 

  75. Glab-Ampai K, Kaewchim K, Thavorasak T, Saenlom T, Thepsawat W, Mahasongkram K, et al. Targeting emerging RNA Viruses by engineered human superantibody to hepatitis C virus RNA-dependent RNA polymerase. Front Microbiol. 2022;13:926929. https://doi.org/10.3389/fmicb.2022.926929.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Montazersaheb S, Hosseiniyan Khatibi SM, Hejazi MS, Tarhriz V, Farjami A, et al. COVID-19 infection: an overview on cytokine storm and related interventions. Virol J. 2022;19(1):92. https://doi.org/10.1186/s12985-022-01814-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wang X, Tang G, Liu Y, Zhang L, Chen B, Han Y, et al. The role of IL-6 in coronavirus, especially in COVID-19. Front Pharmacol. 2022;13:1033674. https://doi.org/10.3389/fphar.2022.1033674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Grunst MW, Uchil PD. Fc effector cross-reactivity: a hidden arsenal against SARS-CoV-2’s evasive maneuvering. Cell Rep Med. 2022;3(2):100540. https://doi.org/10.1016/j.xcrm.2022.100540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chan CEZ, Seah SGK, Chye H, Massey S, Torres M, Lim APC, et al. The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody. PLoS ONE. 2021;16(6):e0253487. https://doi.org/10.1371/journal.pone.0253487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ikewaki N, Kurosawa G, Levy GA, Preethy S, Abraham SJK. Antibody dependent disease enhancement (ADE) after COVID-19 vaccination and beta glucans as a safer strategy in management. Vaccine. 2023;41(15):2427–9. https://doi.org/10.1016/j.vaccine.2023.03.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin. 2020;35(3):266–71. https://doi.org/10.1007/s12250-020-00207-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Abidi E, El Nekidy WS, Alefishat E, Rahman N, Petroianu GA, El-Lababidi R, et al. Tocilizumab and COVID-19: timing of administration and efficacy. Front Pharmacol. 2022;13:825749. https://doi.org/10.3389/fphar.2022.825749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yin JX, Agbana YL, Sun ZS, Fei SW, Zhao HQ, Zhou XN, et al. Increased interleukin-6 is associated with long COVID-19: a systematic review and meta-analysis. Infect Dis Poverty. 2023;12(1):43. https://doi.org/10.1186/s40249-023-01086-z.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Jafrin S, Aziz MA, Islam MS. Elevated levels of pleiotropic interleukin-6 (IL-6) and interleukin-10 (IL-10) are critically involved with the severity and mortality of COVID-19: an updated longitudinal meta-analysis and systematic review on 147 studies. Biomark Insights. 2022;17:11772719221106600. https://doi.org/10.1177/11772719221106600.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Nishimoto N, Kishimoto T. Humanized antihuman IL-6 receptor antibody, tocilizumab. Handb Exp Pharmacol. 2008;181:151–60. https://doi.org/10.1007/978-3-540-73259-4_7.

    Article  CAS  Google Scholar 

  86. U.S. Food and Drug Administration. FDA roundup: December 23, 2022. 2022. https://www.fda.gov/news-events/press-announcements/fda-roundup-december-23-2022. (assessed 2023, Jul 28).

  87. Gupta S, Leaf DE. Tocilizumab in COVID-19: some clarity amid controversy. Lancet. 2021;397(10285):1599–601. https://doi.org/10.1016/S0140-6736(21)00712-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med. 2021;384(1):20–30. https://doi.org/10.1056/NEJMoa2030340.

    Article  CAS  PubMed  Google Scholar 

  89. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383(24):2333–44. https://doi.org/10.1056/NEJMoa2028836.

    Article  CAS  PubMed  Google Scholar 

  90. Kow CS, Hasan SS. The effect of tocilizumab on mortality in hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. 2021;77(8):1089–94. https://doi.org/10.1007/s00228-021-03087-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lin WT, Hung SH, Lai CC, Wang CY, Chen CH. The effect of tocilizumab on COVID-19 patient mortality: a systematic review and meta-analysis of randomized controlled trials. Int Immunopharmacol. 2021;96:107602. https://doi.org/10.1016/j.intimp.2021.107602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Gupta S, Padappayil RP, Bansal A, Daouk S, Brown B. Tocilizumab in patients hospitalized with COVID-19 pneumonia: systematic review and meta-analysis of randomized controlled trials. J Investig Med. 2022;70(1):55–60. https://doi.org/10.1136/jim-2021-002001.

    Article  PubMed  Google Scholar 

  93. Rosas IO, Bräu N, Waters M, Go RC, Malhotra A, Hunter BD, et al. Tocilizumab in patients hospitalised with COVID-19 pneumonia: efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA). EClinicalMedicine. 2022;47:101409. https://doi.org/10.1016/j.eclinm.2022.101409.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Selvaraj V, Khan MS, Bavishi C, Dapaah-Afriyie K, Finn A, Lal A, et al. Tocilizumab in hospitalized patients with COVID-19: a meta analysis of randomized controlled trials. Lung. 2021;199(3):239–48. https://doi.org/10.1007/s00408-021-00451-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Chamlagain R, Shah S, Sharma Paudel B, Dhital R, Kandel B. Efficacy and safety of sarilumab in COVID-19: a systematic review. Interdiscip Perspect Infect Dis. 2021;2021:8903435. https://doi.org/10.1155/2021/8903435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. CORIMUNO-19 Collaborative group. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): an open-label randomised controlled trial. Lancet Rheumatol. 2022;4(1):e24–32. https://doi.org/10.1016/S2665-9913(21)00315-5.

    Article  Google Scholar 

  97. Pacha O, Sallman MA, Evans SE. COVID-19: a case for inhibiting IL-17? Nat Rev Immunol. 2020;20(6):345–6. https://doi.org/10.1038/s41577-020-0328-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Resende GG, da Cruz Lage R, Lobê SQ, Medeiros AF, Costa E Silva AD, NogueiraSá AT, et al. Blockade of interleukin seventeen (IL-17A) with secukinumab in hospitalized COVID-19 patients - the BISHOP study. Infect Dis (Lond). 2022;54(8):591–9. https://doi.org/10.1080/23744235.2022.2066171.

    Article  CAS  PubMed  Google Scholar 

  99. Cavalli G, Larcher A, Tomelleri A, Campochiaro C, Della-Torre E, De Luca G, et al. Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study. Lancet Rheumatol. 2021;3(4):e253–61. https://doi.org/10.1016/S2665-9913(21)00012-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kokkotis G, Kitsou K, Xynogalas I, Spoulou V, Magiorkinis G, Trontzas I, et al. Systematic review with meta-analysis: COVID-19 outcomes in patients receiving anti-TNF treatments. Aliment Pharmacol Ther. 2022;55(2):154–67. https://doi.org/10.1111/apt.16717.

    Article  CAS  PubMed  Google Scholar 

  101. Pandey P, Al Rumaih Z, Kels MJT, Ng E, Kc R, Malley R, et al. Therapeutic targeting of inflammation and virus simultaneously ameliorates influenza pneumonia and protects from morbidity and mortality. Viruses. 2023;15(2):318. https://doi.org/10.3390/v15020318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Hasan MJ, Rabbani R, Anam AM, Huq SMR. Secukinumab in severe COVID-19 pneumonia: does it have a clinical impact? J Infect. 2021;83(1):e11–3. https://doi.org/10.1016/j.jinf.2021.05.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Moreira TG, Gauthier CD, Murphy L, Lanser TB, Paul A, Matos KTF, et al. Nasal administration of anti-CD3 mAb (Foralumab) downregulates NKG7 and increases TGFB1 and GIMAP7 expression in T cells in subjects with COVID-19. Proc Natl Acad Sci U S A. 2023;120(11):e2220272120. https://doi.org/10.1073/pnas.2220272120.

    Article  CAS  Google Scholar 

  104. Rose-John S, Winthrop K, Calabrese L. The role of IL-6 in host defence against infections: immunobiology and clinical implications. Nat Rev Rheumatol. 2017;13(7):399–409. https://doi.org/10.1038/nrrheum.2017.83.

    Article  CAS  PubMed  Google Scholar 

  105. Koritala T, Pattan V, Tirupathi R, Rabaan AA, Al Mutair A, Alhumaid S, et al. Infection risk with the use of interleukin inhibitors in hospitalized patients with COVID-19: a narrative review. Infez Med. 2021;29(4):495–503. https://doi.org/10.53854/liim-2904-1.

  106. Belletti A, Campochiaro C, Marmiere M, Likhvantsev V, Yavorovskiy A, Dagna L, et al. Efficacy and safety of IL-6 inhibitors in patients with COVID-19 pneumonia: a systematic review and meta-analysis of multicentre, randomized trials. Ann Intensive Care. 2021;11(1):152. https://doi.org/10.1186/s13613-021-00941-2.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Kimmig LM, Wu D, Gold M, Pettit NN, Pitrak D, Mueller J, et al. IL-6 Inhibition in critically ill COVID-19 patients is associated with increased secondary infections. Front Med (Lausanne). 2020;7:583897. https://doi.org/10.3389/fmed.2020.583897.

    Article  PubMed  Google Scholar 

  108. Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020;2(8):e474–84. https://doi.org/10.1016/S2665-9913(20)30173-9.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Pettit NN, Nguyen CT, Mutlu GM, Wu D, Kimmig L, Pitrak D, et al. Late onset infectious complications and safety of tocilizumab in the management of COVID-19. J Med Virol. 2021;93(3):1459–64. https://doi.org/10.1002/jmv.26429.

    Article  CAS  PubMed  Google Scholar 

  110. Rubin EJ, Longo DL, Baden LR. Interleukin-6 receptor inhibition in Covid-19 - cooling the inflammatory soup. N Engl J Med. 2021;384(16):1564–5. https://doi.org/10.1056/NEJMe2103108.

    Article  CAS  PubMed  Google Scholar 

  111. Zizzo G, Tamburello A, Castelnovo L, Laria A, Mumoli N, Faggioli PM, et al. Immunotherapy of COVID-19: inside and beyond IL-6 signalling. Front Immunol. 2022;13:795315. https://doi.org/10.3389/fimmu.2022.795315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Muramatsu T. Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners. J Biochem. 2016;159(5):481–90. https://doi.org/10.1093/jb/mvv127.

    Article  CAS  PubMed  Google Scholar 

  113. Knutti N, Huber O, Friedrich K. CD147 (EMMPRIN) controls malignant properties of breast cancer cells by interdependent signaling of Wnt and JAK/STAT pathways. Mol Cell Biochem. 2019;451(1–2):197–209. https://doi.org/10.1007/s11010-018-3406-9.

    Article  CAS  PubMed  Google Scholar 

  114. Dai L, Guinea MC, Slomiany MG, Bratoeva M, Grass GD, Tolliver LB, et al. CD147-dependent heterogeneity in malignant and chemoresistant properties of cancer cells. Am J Pathol. 2013;182(2):577–85. https://doi.org/10.1016/j.ajpath.2012.10.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Pushkarsky T, Zybarth G, Dubrovsky L, Yurchenko V, Tang H, Guo H, et al. CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A. Proc Natl Acad Sci U S A. 2001;98(11):6360–5. https://doi.org/10.1073/pnas.111583198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Zhang MY, Zhang Y, Wu XD, Zhang K, Lin P, Bian HJ, et al. Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum. Blood. 2018;131(10):1111–21. https://doi.org/10.1182/blood-2017-08-802918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. • Wang K, Chen W, Zhang Z, Deng Y, Lian JQ, Du P, et al. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal Transduct Target Ther. 2020;5(1):283. https://doi.org/10.1038/s41392-020-00426-x. (This study repurposed the anti-CD147 antibody for the treatment of SARS-CoV-2.)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Bian H, Zheng ZH, Wei D, Wen A, Zhang Z, Lian JQ, et al. Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial. Signal Transduct Target Ther. 2021;6(1):194. https://doi.org/10.1038/s41392-021-00603-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Yurchenko V, Constant S, Eisenmesser E, Bukrinsky M. Cyclophilin-CD147 interactions: a new target for anti-inflammatory therapeutics. Clin Exp Immunol. 2010;160(3):305–17. https://doi.org/10.1111/j.1365-2249.2010.04115.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Wu J, Chen L, Qin C, Huo F, Liang X, Yang X, et al. CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis. Signal Transduct Target Ther. 2022;7(1):382. https://doi.org/10.1038/s41392-022-01230-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Alegre ML, Tso JY, Sattar HA, Smith J, Desalle F, Cole M, et al. An anti-murine CD3 monoclonal antibody with a low affinity for Fc gamma receptors suppresses transplantation responses while minimizing acute toxicity and immunogenicity. J Immunol. 1995;155(3):1544–55.

    Article  CAS  PubMed  Google Scholar 

  122. van der Woude CJ, Stokkers P, van Bodegraven AA, Van Assche G, Hebzda Z, Paradowski L, et al. Phase I, double-blind, randomized, placebo-controlled, dose-escalation study of NI-0401 (a fully human anti-CD3 monoclonal antibody) in patients with moderate to severe active Crohn’s disease. Inflamm Bowel Dis. 2010;16(10):1708–16. https://doi.org/10.1002/ibd.21252.

    Article  PubMed  Google Scholar 

  123. Oganesyan V, Damschroder MM, Woods RM, Cook KE, Wu H, Dall’acqua WF. Structural characterization of a human Fc fragment engineered for extended serum half-life. Mol Immunol. 2009;46(8–9):1750–5. https://doi.org/10.1016/j.molimm.2009.01.026.

    Article  CAS  PubMed  Google Scholar 

  124. Oganesyan V, Gao C, Shirinian L, Wu H, Dall’Acqua WF. Structural characterization of a human Fc fragment engineered for lack of effector functions. Acta Crystallogr D Biol Crystallogr. 2008;64(Pt 6):700–4. https://doi.org/10.1107/S0907444908007877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Schlothauer T, Herter S, Koller CF, Grau-Richards S, Steinhart V, Spick C, et al. Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions. Protein Eng Des Sel. 2016;29(10):457–66. https://doi.org/10.1093/protein/gzw040.

    Article  CAS  PubMed  Google Scholar 

  126. Zhang D, Goldberg MV, Chiu ML. Fc engineering approaches to enhance the agonism and effector functions of an anti-OX40 antibody. J Biol Chem. 2016;291(53):27134–46. https://doi.org/10.1074/jbc.M116.757773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Shi R, Shan C, Duan X, Chen Z, Liu P, Song J, et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature. 2020;584(7819):120–4. https://doi.org/10.1038/s41586-020-2381-y.

    Article  CAS  PubMed  Google Scholar 

  128. Brambell FW. The transmission of immunity from mother to young and the catabolism of immunoglobulins. Lancet. 1966;2(7473):1087–93. https://doi.org/10.1016/s0140-6736(66)92190-8.

    Article  CAS  PubMed  Google Scholar 

  129. Ramdani Y, Lamamy J, Watier H, Gouilleux-Gruart V. Monoclonal antibody engineering and design to modulate FcRn activities: a comprehensive review. Int J Mol Sci. 2022;23(17):9604. https://doi.org/10.3390/ijms23179604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Pyzik M, Sand KMK, Hubbard JJ, Andersen JT, Sandlie I, Blumberg RS. The neonatal Fc receptor (FcRn): a misnomer? Front Immunol. 2019;10:1540. https://doi.org/10.3389/fimmu.2019.01540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Lee CH, Kang TH, Godon O, Watanabe M, Delidakis G, Gillis CM, et al. An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence. Nat Commun. 2019;10(1):5031. https://doi.org/10.1038/s41467-019-13108-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Winkler ES, Gilchuk P, Yu J, Bailey AL, Chen RE, Chong Z, et al. Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. Cell. 2021;184(7):1804-1820.e16. https://doi.org/10.1016/j.cell.2021.02.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Gorman MJ, Patel N, Guebre-Xabier M, Zhu AL, Atyeo C, Pullen KM, et al. Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination. Cell Rep Med. 2021;2(9):100405. https://doi.org/10.1016/j.xcrm.2021.100405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zohar T, Loos C, Fischinger S, Atyeo C, Wang C, Slein MD, et al. Compromised humoral functional evolution tracks with SARS-CoV-2 mortality. Cell. 2020;183(6):1508-1519.e12. https://doi.org/10.1016/j.cell.2020.10.052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Yamin R, Jones AT, Hoffmann HH, Schäfer A, Kao KS, Francis RL, et al. Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy. Nature. 2021;599(7885):465–70. https://doi.org/10.1038/s41586-021-04017-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Chen B, Vousden KA, Naiman B, Turman S, Sun H, Wang S, et al. Humanised effector-null FcγRIIA antibody inhibits immune complex-mediated proinflammatory responses. Ann Rheum Dis. 2019;78(2):228–37. https://doi.org/10.1136/annrheumdis-2018-213523.

    Article  CAS  PubMed  Google Scholar 

  137. ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2022;10(10):972–84. https://doi.org/10.1016/S2213-2600(22)00215-6.

    Article  Google Scholar 

  138. Merigeon EY, Yang D, Ihms EA, Bassit LC, Fitzpatrick EA, Jonsson CB, et al. An ACE2-IgG4 Fc fusion protein demonstrates strong binding to all tested SARS-CoV-2 variants and reduced lung inflammation in animal models of SARS-CoV-2 and influenza. Pathog Immun. 2022;7(1):104–21. https://doi.org/10.20411/pai.v7i1.491.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Qiang M, Ma P, Li Y, Liu H, Harding A, Min C, et al. Neutralizing antibodies to SARS-CoV-2 selected from a human antibody library constructed decades ago. Adv Sci (Weinh). 2022;9(1):e2102181. https://doi.org/10.1002/advs.202102181.

    Article  CAS  PubMed  Google Scholar 

  140. Loo YM, McTamney PM, Arends RH, Abram ME, Aksyuk AA, Diallo S, et al. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med. 2022;14(635):eabl8124. https://doi.org/10.1126/scitranslmed.abl8124.

    Article  CAS  PubMed  Google Scholar 

  141. Wu X, Li N, Wang G, Liu W, Yu J, Cao G, et al. Pharmacokinetics, and immunogenicity of a Novel SARS-CoV-2 neutralizing antibody, Etesevimab, in Chinese healthy adults: a randomized, double-blind, placebo-controlled, first-in-human phase 1 study. Antimicrob Agents Chemother. 2021;65(8): e0035021. https://doi.org/10.1128/AAC.00350-21.

    Article  PubMed  Google Scholar 

  142. Igawa T, Ishii S, Tachibana T, Maeda A, Higuchi Y, Shimaoka S, et al. Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization. Nat Biotechnol. 2010;28(11):1203–7. https://doi.org/10.1038/nbt.1691.

    Article  CAS  PubMed  Google Scholar 

  143. Petkova SB, Akilesh S, Sproule TJ, Christianson GJ, Al Khabbaz H, Brown AC, et al. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol. 2006;18(12):1759–69. https://doi.org/10.1093/intimm/dxl110.

    Article  CAS  PubMed  Google Scholar 

  144. Bournazos S, Corti D, Virgin HW, Ravetch JV. Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection. Nature. 2020;588(7838):485–90. https://doi.org/10.1038/s41586-020-2838-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, Songa EB, et al. Naturally occurring antibodies devoid of light chains. Nature. 1993;363(6428):446–8. https://doi.org/10.1038/363446a0.

    Article  CAS  PubMed  Google Scholar 

  146. Muyldermans S. Nanobodies: natural single-domain antibodies. Annu Rev Biochem. 2013;82:775–97. https://doi.org/10.1146/annurev-biochem-063011-092449.

    Article  CAS  PubMed  Google Scholar 

  147. Kunz P, Zinner K, Mücke N, Bartoschik T, Muyldermans S, Hoheisel JD. The structural basis of nanobody unfolding reversibility and thermoresistance. Sci Rep. 2018;8(1):7934. https://doi.org/10.1038/s41598-018-26338-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Mohseni A, Molakarimi M, Taghdir M, Sajedi RH, Hasannia S. Exploring single-domain antibody thermostability by molecular dynamics simulation. J Biomol Struct Dyn. 2019;37(14):3686–96. https://doi.org/10.1080/07391102.2018.1526116.

    Article  CAS  PubMed  Google Scholar 

  149. Hussack G, Mackenzie CR, Tanha J. Characterization of single-domain antibodies with an engineered disulfide bond. Methods Mol Biol. 2012;911:417–29. https://doi.org/10.1007/978-1-61779-968-6_25.

    Article  CAS  PubMed  Google Scholar 

  150. Chen J, He QH, Xu Y, Fu JH, Li YP, Tu Z, et al. Nanobody medicated immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein. Talanta. 2016;147:523–30. https://doi.org/10.1016/j.talanta.2015.10.027.

    Article  CAS  PubMed  Google Scholar 

  151. Kaewchim K, Glab-Ampai K, Mahasongkram K, Saenlom T, Thepsawat W, Chulanetra M, et al. Neutralizing and enhancing epitopes of the SARS-CoV-2 receptor-binding domain (RBD) identified by nanobodies. Viruses. 2023;15(6):1252. https://doi.org/10.3390/v15061252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Ye G, Gallant J, Zheng J, Massey C, Shi K, Tai W, et al. The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates. Elife. 2021;10:e64815. https://doi.org/10.7554/eLife.64815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Chi X, Zhang X, Pan S, Yu Y, Shi Y, Lin T, et al. An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants. Signal Transduct Target Ther. 2022;7(1):44. https://doi.org/10.1038/s41392-022-00912-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Ettich J, Werner J, Weitz HT, Mueller E, Schwarzer R, Lang PA, et al. A hybrid soluble gp130/spike-nanobody fusion protein simultaneously blocks interleukin-6 trans-signaling and cellular infection with SARS-CoV-2. J Virol. 2022;96(4):e0162221. https://doi.org/10.1128/JVI.01622-21.

    Article  PubMed  Google Scholar 

  155. Bertoglio F, Meier D, Langreder N, Steinke S, Rand U, Simonelli L, et al. SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface. Nat Commun. 2021;12(1):1577. https://doi.org/10.1038/s41467-021-21609-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Dean AQ, Stauft CB, Twomey JD, Tan J, Varani L, Wang TT, et al. Comparative assessment of the binding and neutralisation activity of bispecific antibodies against SARS-CoV-2 Variants. Antib Ther. 2022;6(1):49–58. https://doi.org/10.1093/abt/tbac032.

    Article  CAS  PubMed  Google Scholar 

  157. De Gasparo R, Pedotti M, Simonelli L, Nickl P, Muecksch F, Cassaniti I, et al. Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice. Nature. 2021;593(7859):424–8. https://doi.org/10.1038/s41586-021-03461-y.

    Article  CAS  PubMed  Google Scholar 

  158. Yuan M, Chen X, Zhu Y, Dong X, Liu Y, Qian Z, et al. A bispecific antibody targeting RBD and S2 potently neutralizes SARS-CoV-2 omicron and other variants of concern. J Virol. 2022;96(16):e0077522. https://doi.org/10.1128/jvi.00775-22.

    Article  CAS  PubMed  Google Scholar 

  159. Lim SA, Gramespacher JA, Pance K, Rettko NJ, Solomon P, Jin J, et al. Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2. MAbs. 2021;13(1):1893426. https://doi.org/10.1080/19420862.2021.1893426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Misasi J, Wei RR, Wang L, Pegu A, Wei CJ, Oloniniyi OK, et al. A multispecific antibody prevents immune escape and confers pan-SARS-CoV-2 neutralization. bioRxiv [Preprint]. 2022;2022.07.29.502029. https://doi.org/10.1101/2022.07.29.502029.

  161. Liu H, Wu L, Liu B, Xu K, Lei W, Deng J, et al. Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice. Cell Rep Med. 2023;4(2):100918. https://doi.org/10.1016/j.xcrm.2023.100918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Panda M, Kalita E, Singh S, Kumar K, Prajapati VK. Nanobody-peptide-conjugate (NPC) for passive immunotherapy against SARS-CoV-2 variants of concern (VoC): a prospective pan-coronavirus therapeutics. Mol Divers. 2022;1–27. https://doi.org/10.1007/s11030-022-10570-x.

  163. Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, et al. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science. 2020;370(6523):1473–9. https://doi.org/10.1126/science.abe3255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Leach A, Miller A, Bentley E, Mattiuzzo G, Thomas J, McAndrew C, et al. Application of a method for engineering multivalent antibodies to substantially enhance functional affinity of clinical trial anti-SARS-CoV-2 antibodies. Research Square [Preprint]. 2021. https://doi.org/10.21203/rs.3.rs-259484/v1.

  165. Rujas E, Kucharska I, Tan YZ, Benlekbir S, Cui H, Zhao T, et al. Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers. Nat Commun. 2021;12(1):3661. https://doi.org/10.1038/s41467-021-23825-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Lu Y, Li Q, Fan H, Liao C, Zhang J, Hu H, et al. A multivalent and thermostable nanobody neutralizing SARS-CoV-2 omicron (B.1.1.529). Int J Nanomedicine. 2023;18:353–67. https://doi.org/10.2147/IJN.S387160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Ibrahim M, Ramadan E, Elsadek NE, Emam SE, Shimizu T, Ando H, et al. Polyethylene glycol (PEG): the nature, immunogenicity, and role in the hypersensitivity of PEGylated products. J Control Release. 2022;351:215–30. https://doi.org/10.1016/j.jconrel.2022.09.031.

    Article  CAS  PubMed  Google Scholar 

  168. Pillarsetty N, Carter LM, Lewis JS, Reiner T. Oncology-inspired treatment options for COVID-19. J Nucl Med. 2020;61(12):1720–3. https://doi.org/10.2967/jnumed.120.249748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Tu B, Gao Y, An X, Wang H, Huang Y. Localized delivery of nanomedicine and antibodies for combating COVID-19. Acta Pharm Sin B. 2023;13(5):1828–46. https://doi.org/10.1016/j.apsb.2022.09.011.

    Article  CAS  PubMed  Google Scholar 

  170. Cruz-Teran C, Tiruthani K, McSweeney M, Ma A, Pickles R, Lai SK. Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy. Adv Drug Deliv Rev. 2021;169:100–17. https://doi.org/10.1016/j.addr.2020.12.004.

    Article  CAS  PubMed  Google Scholar 

  171. Yu J, Uzuner U, Long B, Wang Z, Yuan JS, Dai SY. Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: mechanisms on SARS-CoV-2 immune escape. iScience. 2023;26(4):106282. https://doi.org/10.1016/j.isci.2023.106282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Kapingidza B, Marston DJ, Harris C, Wrapp D, Winters K, Rhodes B, et al. Engineered immunogens to expose conserved epitopes targeted by broad coronavirus antibodies. bioRxiv [Preprint]. 2023;28:2023.02.27.530277. https://doi.org/10.1101/2023.02.27.530277.

  173. Fassi EMA, Manenti M, Citarella A, Dei Cas M, Casati S, Micale N, et al. Computational design, synthesis, and biophysical evaluation of β-amido boronic acids as SARS-CoV-2 Mpro inhibitors. Molecules. 2023;28(5):2356. https://doi.org/10.3390/molecules28052356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Center of Research Excellence in Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Monrat Chulanetra

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Chulanetra, M. Engineered Therapeutic Antibody Against SARS-CoV-2. Curr Clin Micro Rpt 10, 222–235 (2023). https://doi.org/10.1007/s40588-023-00212-7

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