Frontier Therapeutics and Vaccine Strategies for SARS-CoV-2 (COVID-19): A Review

  • Amirhossein SHEIKHSHAHROKH Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  • Reza RANJBAR Mail Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
  • Elnaz SAEIDI Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  • Farhad SAFARPOOR DEHKORDI Halal Research Center of IRI, FDA, Tehran, Iran
  • Mohammad HEIAT Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran
  • Payam GHASEMI-DEHKORDI Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  • Hamed GOODARZI Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
COVID-19;, Immunotherapy;, ACE2;, S protein;, Vaccines


COVID-19 is considered as the third human coronavirus and has a high potential for transmission. Fast public health interventions through antibodies, anti-virals or novel vaccine strategies to control the virus and disease transmission have been extremely followed. SARS-CoV-2 shares about 79% genomic similarity with SARS-CoV and approximately 50% with MERS-CoV. Based on these similarities, prior knowledge in treating SARS-CoV and MERS-CoV can be used as the basis of majority of the alternatives for controlling SARS-CoV-2. Immunotherapy is an effective strategy for clinical treatment of infectious diseases such as SARS-CoV-2. Passive antibody therapy, which decreases the virus replication and disease severity, is assessed as an effective therapeutic approach to control SARS-CoV-2 epidemics. The close similarity between SARS-CoV-2 genome with the SARS-CoV genome caused both coronaviruses to bind to the same angiotensin-converting enzyme 2 (ACE2) receptors that found in the human lung. There are several strategies to develop SARS-CoV-2 vaccines, which the majority of them are based on those developed previously for SARS-CoV. The interaction between the spike (S) protein of SARS-CoV-2 and ACE2 on the host cell surface leads to the initiation of SARS-CoV-2 infection. S protein, which is the main inducer of neutralizing antibodies, has been targeted by most of these strategies. Vaccines that induce an immune response against the S protein to inhibit its binding with the host ACE2 receptor, can be considered as effective vaccines against SARS-CoV-2. Here, we aimed to review frontier therapeutics and vaccination strategies for SARS-CoV-2 (COVID-19).



1. Gorbalenya AE (2020). Severe acute respira-tory syndrome-related coronavirus–The species and its viruses, a statement of the Coronavirus Study Group. Cold Spring Harbor Laboratory.
2. Mubarak A, Alturaiki W, Hemida MG (2019). Middle east respiratory syndrome coronavirus (MERS-CoV): infection, immunological response, and vaccine de-velopment. J Immunol Res, 2019: 1-11.
3. Cui J, Li F, Shi Z-L (2019). Origin and evo-lution of pathogenic coronaviruses. Nat Rev Microbiol, 17 (3): 181-92.
4. Carlos WG, Dela Cruz CS et al (2020). Nov-el wuhan (2019-nCoV) coronavirus. Am J Respir Crit Care Med, 201(4): P7-P8.
5. Vijgen L, Keyaerts E, Moës E et al (2005). Development of one-step, real-time, quantitative reverse transcriptase PCR as-says for absolute quantitation of human coronaviruses OC43 and 229E. J Clin Mi-crobiol, 43 (11): 5452-6.
6. Lu R, Zhao X, Li J et al (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 395(10224): 565-74.
7. Weiss SR, Leibowitz JL (2011). Coronavirus pathogenesis. In: Advances in Virus Re-search. Ed K Maramorosch, AJ Shatkin, AF Murphy. Elsevier, 32 Jamestown Road, London, NW1 7BY, UK. 85-164.
8. Li F (2016). Structure, function, and evolu-tion of coronavirus spike proteins. Annu Rev Virol, 3: 237-61.
9. Xia S, Liu Q, Wang Q et al (2014). Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein. Virus Res, 194 (2014): 200-10.
10. Lu G, Hu Y, Wang Q et al (2013). Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature, 500 (7461): 227-31.
11. Al-Qahtani AA, Lyroni K, Aznaourova M et al (2017). Middle east respiratory syn-drome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ. Oncotarget, 8 (6): 9053-66.
12. Lu H (2020). Drug treatment options for the 2019-new coronavirus (2019-nCoV). Bi-osci Trends, 14 (1): 69-71.
13. Pillaiyar T, Meenakshisundaram S, Manick-am M (2020). Recent discovery and de-velopment of inhibitors targeting coro-naviruses. Drug Discov Today,
14. Graham RL, Donaldson EF, Baric RS (2013). A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol, 11 (12): 836-48.
15. Sui J, Li W, Roberts A et al (2005). Evalua-tion of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J Virol, 79 (10): 5900-6.
16. Marasco WA, Sui J (2007). The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol, 25 (12): 1421-34.
17. Group TPIW, Team M-NPIS (2016). A ran-domized, controlled trial of ZMapp for Ebola virus infection. N Engl J Med, 375 (15): 1448-56.
18. Caskey M, Klein F, Lorenzi JC et al (2015). Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature, 522 (7557): 487-491.
19. Widjaja I, Wang C, van Haperen R et al (2019). Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glyco-protein. Emerg Microbes Infect, 8 (1): 516-30.
20. Goo J, Jeong Y, Park Y-S et al (2020). Char-acterization of novel monoclonal anti-bodies against MERS-coronavirus spike protein. Virus Res, 278:197863.
21. Dandekar AA, Perlman S (2005). Immuno-pathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol, 5 (12): 917-27.
22. Du L, Yang Y, Zhou Y et al (2017). MERS-CoV spike protein: a key target for antivi-rals. Expert Opin Ther Targets, 21 (2): 131-43.
23. Song Z, Xu Y, Bao L et al (2019). From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses, 11 (1): 59.
24. Walls AC, Park Y-J, Tortorici MA et al (2020). Structure, function, and antigenici-ty of the SARS-CoV-2 spike glycoprotein. Cell, 181 (2): 281-92.
25. Zeng L-P, Ge X-Y, Peng C et al (2017). Cross-neutralization of SARS corona-virus-specific antibodies against bat SARS-like coronaviruses. Sci China Life Sci, 60 (12): 1399-402.
26. Coughlin MM, Prabhakar BS (2012). Neu-tralizing human monoclonal antibodies to severe acute respiratory syndrome coro-navirus: target, mechanism of action, and therapeutic potential. Rev Med Virol, 22 (1): 2-17.
27. Schroeder Jr HW, Cavacini L (2010). Struc-ture and function of immunoglobulins. J Allergy Clin Immunol, 125 (2): S41-S52.
28. Sparrow E, Friede M, Sheikh M et al (2017). Therapeutic antibodies for infectious dis-eases. Bull World Health Org, 95 (3): 235-7.
29. Demurtas OC, Massa S, Illiano E et al (2016). Antigen production in plant to tackle infectious diseases flare up: the case of SARS. Front Plant Sci, 7: 54.
30. Hiatt A, Whaley K, Zeitlin L (2015). Plant-derived monoclonal antibodies for pre-vention and treatment of infectious dis-ease. In: Antibodies for Infectious Diseases: Ed, James E. Crowe Jr. Diana Boraschi Rino Rappuoli. Microbiol Spectr, mBio press, Washington, D.C., USA. 413-25.
31. Sainsbury F (2020). Innovation in plant-based transient protein expression for in-fectious disease prevention and prepar-edness. Curr Opin Biotechnol, 61: 110-15.
32. Shanmugaraj B, Malla A, Phoolcharoen W (2020). Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development. Pathogens, 9 (2): 148.
33. Cohen J (2020). New coronavirus threat gal-vanizes scientists. Science, 367 (6477): 492-3
34. Seesuay W, Jittavisutthikul S, Sae-Lim N et al (2018). Human transbodies that interfere with the functions of Ebola virus VP35 protein in genome replication and tran-scription and innate immune antagonism. Emerg Microbes Infect, 7(1):41.
35. Mupapa K, Massamba M, Kibadi K et al (1999). Treatment of Ebola hemorrhagic fever with blood transfusions from con-valescent patients. J Infect Dis, 1:S18-23.
36. Arabi Y, Balkhy H, Hajeer AH et al (2015). Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus, 19;4:709.
37. Jiang S, Bottazzi ME, Du L et al (2012). Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respira-tory syndrome. Expert Rev Vaccines, 11 (12): 1405-13.
38. Chen W-H, Strych U, Hotez PJ et al (2020). The SARS-CoV-2 Vaccine Pipeline: an Overview. Curr Trop Med Rep, 1-4.
39. Yang Z-y, Kong W-p, Huang Y et al (2004). A DNA vaccine induces SARS corona-virus neutralization and protective im-munity in mice. Nature, 428 (6982): 561-4.
40. Ji W, Wang W, Zhao X, et al (2020). Cross-species transmission of the newly identi-fied coronavirus 2019-nCoV. J Med Virol, 92 (4): 433-40.
41. Schindewolf C, Menachery VD (2019). Middle east respiratory syndrome vaccine candidates: cautious optimism. Viruses, 17;11(1).
42. Du L, He Y, Zhou Y et al (2009). The spike protein of SARS-CoV—a target for vac-cine and therapeutic development. Nat Rev Microbiol, 7 (3): 226-36.
43. Chen R, Fu J, Hu J et al (2020). Identification of the immunodominant neutralizing re-gions in the spike glycoprotein of porcine deltacoronavirus. Virus Res, 276: 197834.
44. Buchholz UJ, Bukreyev A, Yang L et al (2004). Contributions of the structural proteins of severe acute respiratory syn-drome coronavirus to protective immuni-ty. Proc Natl Acad Sci U S A, 101 (26): 9804-9.
45. Kim MH, Kim HJ, Chang J (2019). Superior immune responses induced by intranasal immunization with recombinant adenovi-rus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus. PLoS One, 14(7):e0220196.
46. Coleman CM, Liu YV, Mu H et al (2014). Purified coronavirus spike protein nano-particles induce coronavirus neutralizing antibodies in mice. Vaccine, 32 (26): 3169-74.
47. Jiang S, He Y, Liu S (2005). SARS vaccine development. Emerg Infect Dis, 11 (7): 1016-20.
48. Chen W-H, Chag SM, Poongavanam MV et al (2017). Optimization of the production process and characterization of the yeast-expressed SARS-CoV recombinant re-ceptor-binding domain (RBD219-N1), a SARS vaccine candidate. J Pharm Sci, 106 (8): 1961-70.
49. Chen W-H, Du L, Chag SM et al (2014). Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate. Hum Vaccin Immunother, 10 (3): 648-58.
50. Li E, Yan F, Huang P, Xu S, Li G, Liu C et al (2020). Characterization of the immune response of MERS-CoV vaccine candi-dates derived from two different vectors in mice. Viruses, 12 (1): 125.
51. Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, Gao GF (2017). T-cell immunity of SARS-CoV: Implications for vaccine devel-opment against MERS-CoV. Antiviral Res, 137 (2017): 82-92.
52. Jiang S, Du L, Shi Z (2020). An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect, 9 (1): 275-7.
53. Yu F, Du L, Ojcius DM et al (2020). Measures for diagnosing and treating in-fections by a novel coronavirus respon-sible for a pneumonia outbreak originat-ing in Wuhan, China. Microbes Infect, 22 (2): 74-9.
54. Liu W, Morse JS, Lalonde T et al (2020). Learning from the past: possible urgent prevention and treatment options for se-vere acute respiratory infections caused by 2019-nCoV. Chembiochem, 21 (5): 730-8.
55. Baruah V, Bose S (2020). Immunoinformat-ics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV. J Med Virol, 92 (5): 495-500.
56. Shi J, Zhang J, Li S et al (2015). Epitope-based vaccine target screening against highly pathogenic MERS-CoV: an in sili-co approach applied to emerging infec-tious diseases. PLoS One, 10 (12): e0144475.
57. Xie Q, He X, Yang F, Liu X, Li Y, Liu Yet al (2017). Analysis of the genome se-quence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus. IEEE/ACM Trans Comput Biol Bioinform. 15 (4): 1344-50.
58. Bijlenga G (2005). Proposal for vaccination against SARS coronavirus using avian in-fectious bronchitis virus strain H from The Netherlands. J Infect, 51 (3): 263-5.
59. Zhang L, Liu Y (2020). Potential interven-tions for novel coronavirus in China: A systematic review. J Med Virol, 92 (5): 479-90.
60. Schwartz DA, Graham AL (2020). Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-ncov infecting pregnant women: lessons from SARS, MERS, and other human coronavirus in-fections. Viruses, 12 (2): 194-210.
61. Pang J, Wang MX, Ang IYH et al (2020). Potential rapid diagnostics, vaccine and therapeutics for 2019 novel Coronavirus (2019-ncoV): a systematic review. J Clin Med, 9 (3): 623-56.
62. Rutschman AS (2020). The Intellectual Prop-erty of Vaccines: Takeaways from Recent Infectious Disease Outbreaks. Mich Law Rev, 2020: 1-13.
63. Challener CA (2020). Can Vaccine Devel-opment Be Safely Accelerated. Pharm Technol, 44 (4): 22-26.
How to Cite
SHEIKHSHAHROKH A, RANJBAR R, SAEIDI E, SAFARPOOR DEHKORDI F, HEIAT M, GHASEMI-DEHKORDI P, GOODARZI H. Frontier Therapeutics and Vaccine Strategies for SARS-CoV-2 (COVID-19): A Review. Iran J Public Health. 49(Supple 1):18-29.
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