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

  • Amirhossein SHEIKHSHAHROKH State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China AND 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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