Next-Generation Vaccines and Antiviral Platforms: Molecular Advancements in the Struggle against Emerging Zoonotic and Viral Diseases

Document Type : Review Article

Authors

1 Department of Agriculture, Jo.C, Islamic Azad University, Jouybar, Iran

2 Nigde Omer Halisdemir University

3 Department of Biology, College of Science, University of Zakho, Duhok, Iraq

4 Department of Obstetrics and Gynecology, Batman Training and Research Hospital, Batman, Turkey

5 Allergy and Asthma Center, Blue Area, Islamabad, Pakistan. Former Chief, Clinical and Tropical Diseases Research Division, National Institute of Health, Islamabad. Former HOD Allergy & Immunology, NIH, Islamabad, Pakistan

10.32592/ARI.2025.80.3.649

Abstract

The ongoing occurrence of zoonotic and viral diseases, such as SARS-CoV-2, H5N1, Nipah, and Ebola viruses, underscores the requirement for transformative innovations in vaccine and antiviral development. Classic vaccine technologies like inactivated or live-attenuated virus products have lengthy production cycles, cold-chain storage, and are poorly suited to reacting rapidly to emerging threats This review synthesizes the most recent advances in molecular virology, immunogen design, and biotechnology that will propel the next generation of prevention and treatment tools. We begin with the genomic and structural characteristics of high-consequence zoonotic viruses, highlighting the molecular determinants for virulence, host switching, and immune evasion. The review then provides a comparative review of the emerging vaccine platforms such as mRNA, DNA, viral vector, subunit, and inactivated vaccines based on design rationale, delivery systems, immunogenicity profiles, and global rollouts. At the same time, molecular mechanisms of antiviral drugs acting against viral polymerases, proteases, and entry mechanisms are discussed, and the new challenge of resistance evolution is emphasized. We also highlight recently developed molecular diagnostic tools like CRISPR-based tools, nanopore sequencing, and isothermal amplification technologies that are transforming real-time pathogen diagnosis in veterinary and human medicine. Last, the One Health aspect is introduced through veterinary applications of vaccines to zoonotic spillover prevention and antimicrobial resistance. In conclusion, this review gives a vision-orientated account of molecular strategies that bring together human and animal medicine to combat future pandemics. Our aggregated tables and visualizations are an asset for researchers, clinicians, and policymakers interested in the improvement of epidemic preparedness and cross-species disease surveillance.

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References

  1. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discovery. 2022;12(1):31-46.
  2. Morris CE, Moury B. Revisiting the concept of host range of plant pathogens. Annual Review of Phytopathology. 2019;57(1):63-90.
  3. Kayser V, Ramzan I. Vaccines and vaccination: history and emerging issues. Human Vaccines & Immunotherapeutics. 2021;17(12):5255-5268.
  4. Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, Akram M, Riaz M, Rasool G, et al. A review: mechanism of action of antiviral drugs. International Journal of Immunopathology and Pharmacology. 2021;35:20587384211002621.
  5. Recht J, Schuenemann VJ, Sánchez-Villagra MR. Host diversity and origin of zoonoses: the ancient and the new. Animals. 2020;10(9):1672.
  6. Chandra S, Wilson JC, Good D, Wei MQ. mRNA vaccines: a new era in vaccine development. Oncology Research. 2024;32(10):1543.
  7. Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nature Reviews Materials. 2021;6(12):1078-1094.
  8. Omer SB, Yildirim I, Forman HP. Herd immunity and implications for SARS-CoV-2 control. Journal of the American Medical Association. 2020;324(20):2095-2096.
  9. Kaufmann SH, Dorhoi A, Hotchkiss RS, Bartenschlager R. Host-directed therapies for bacterial and viral infections. Nature Reviews Drug Discovery. 2018;17(1):35-56.
  10. Houseini ST, Nemati F, Sattari A, Azadeh M, Bishehkolaei R. Design of crRNA to regulate microRNAs related to metastasis in colorectal cancer using CRISPR-C2c2 (Cas13a) technique. Cell Journal. 2023;25(5):354.
  11. Destoumieux-Garzón D, Mavingui P, Boetsch G, Boissier J, Darriet F, Duboz P, et al. The One Health concept: 10 years old and a long road ahead. Frontiers in Veterinary Science. 2018;5:14.
  12. Boni MF, Lemey P, Jiang X, Lam TT, Perry BW, Castoe TA, et al. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Nature Microbiology. 2020;5(11):1408-1417.
  13. Rodrigue V, Gravagna K, Yao J, Nafade V, Basta NE. Current progress towards prevention of Nipah and Hendra disease in humans: a scoping review of vaccine and monoclonal antibody candidates being evaluated in clinical trials. Tropical Medicine and International Health. 2024;29(5):354-364.
  14. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiology. 2020;5(4):562-569.
  15. Hoffmann M, Kleine-Weber H, Pöhlmann S. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Molecular Cell. 2020;78(4):779-784.
  16. Li JY, Liao CH, Wang Q, Tan YJ, Luo R, Qiu Y, Ge XY. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Research. 2020;286:198074.
  17. Kim D, Lee JY, Yang JS, Kim JW, Kim VN, Chang H. The architecture of SARS-CoV-2 transcriptome. Cell. 2020;181(4):914-921.
  18. Di Giorgio S, Martignano F, Torcia MG, Mattiuz G, Conticello SG. Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2. Science Advances. 2020;6(25):eabb5813.
  19. Sun H, Gu R, Tang T, Rai KR, Chen JL. Current perspectives on functional involvement of micropeptides in virus–host interactions. International Journal of Molecular Sciences. 2025;26(8):3651.
  20. Grubaugh ND, Ladner JT, Lemey P, Pybus OG, Rambaut A, Holmes EC, et al. Tracking virus outbreaks in the twenty-first century. Nature Microbiology. 2019;4(1):10-19.
  21. Liu C, Shi Q, Huang X, Koo S, Kong N, Tao W. mRNA-based cancer therapeutics. Nature Reviews Cancer. 2023;23(8):526–543.
  22. Park JW, Lagniton PN, Liu Y, Xu RH. mRNA vaccines for COVID-19: what, why and how. International Journal of Biological Sciences. 2021;17(6):1446.
  23. PREVAC Study Team. Randomized trial of vaccines for Zaire Ebola virus disease. The New England Journal of Medicine. 2022;387(26):2411–2424.
  24. Tukhvatulin AI, Dolzhikova IV, Dzharullaeva AS, Grousova DM, Kovyrshina AV, Zubkova OV, et al. Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study. Frontiers in Immunology. 2023;14:1228461.
  25. Xiao W, Jiang W, Chen Z, Huang Y, Mao J, Zheng W, Hu Y, Shi J. Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines. Signal Transduction and Targeted Therapy. 2025;10(1):74.
  26. Zhai Y, Han Y, Wang W, Tan W. Advancements in Mpox vaccine development: A comprehensive review of global progress and recent data. Biomedical and Environmental Sciences. 2025;38(2):248–254.
  27. Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, et al. Remdesivir: a review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS Central Science. 2020;6(5):672–683.
  28. Dunning J, Thwaites RS, Openshaw PJ. Seasonal and pandemic influenza: 100 years of progress, still much to learn. Mucosal Immunology. 2020;13(4):566–573.
  29. Abbott TR, Dhamdhere G, Liu Y, Lin X, Goudy L, Zeng L, et al. Development of CRISPR as an antiviral strategy to combat SARS-CoV-2 and influenza. Cell. 2020;181(4):865–876.
  30. Li Z, Li Z, Cheng X, Wang S, Wang X, Ma S, et al. Intrinsic targeting of host RNA by Cas13 constrains its utility. Nature Biomedical Engineering. 2024;8(2):177–192.
  31. Venu E, Ramya A, Babu PL, Srinivas B, Kumar S, Reddy NK, et al. Exogenous dsRNA-mediated RNAi: mechanisms, applications, delivery methods and challenges in the induction of viral disease resistance in plants. Viruses. 2024;17(1):49.
  32. Wei N, Zheng B, Niu J, Chen T, Ye J, Si Y, Cao S. Rapid detection of genotype II African swine fever virus using CRISPR Cas13a-based lateral flow strip. Viruses. 2022;14(2):179.
  33. Joung J, Ladha A, Saito M, Segel M, Bruneau R, Huang ML, et al. Point-of-care testing for COVID-19 using SHERLOCK diagnostics. medRxiv. 2020. https://doi.org/10.1101/2020.05.04.20091231
  34. Myhrvold C, Freije CA, Gootenberg JS, Abudayyeh OO, Metsky HC, Durbin AF, et al. Field-deployable viral diagnostics using CRISPR-Cas13. Science. 2018;360(6387):444–448.
  35. Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, et al. CRISPR–Cas12-based detection of SARS-CoV-2. Nature Biotechnology. 2020;38(7):870–874.
  36. Nzelu CO, Kato H, Peters NC. Loop-mediated isothermal amplification (LAMP): an advanced molecular point-of-care technique for the detection of Leishmania infection. Advances in Medical Imaging, Detection and Diagnosis. 2023:755–781.
  37. Zhang Y, Hunt EA, Tamanaha E, Corrêa IR Jr, Tanner NA. Improved visual detection of DNA amplification using pyridylazophenol metal sensing dyes. Communications Biology. 2022;5(1):999.
  38. Lobato IM, O'Sullivan CK. Recombinase polymerase amplification: basics, applications and recent advances. Trends in Analytical Chemistry. 2018;98:19–35.
  39. Mohanraj J, Durgalakshmi D, Rakkesh RA, Balakumar S, Rajendran S, Karimi-Maleh H. Facile synthesis of paper-based graphene electrodes for point of care devices: a double stranded DNA (dsDNA) biosensor. Journal of Colloid and Interface Science. 2020;566:463–472.
  40. Lino C, Barrias S, Chaves R, Adega F, Martins-Lopes P, Fernandes JR. Biosensors as diagnostic tools in clinical applications. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2022;1877(3):188726.
  41. Kim J, Campbell AS, de Ávila BE, Wang J. Wearable biosensors for healthcare monitoring. Nature Biotechnology. 2019;37(4):389-406.
  42. Fatima M, An T, Park PG, Hong KJ. Advancements and challenges in addressing zoonotic viral infections with epidemic and pandemic threats. Viruses. 2025;17(3):352.
  43. Mao W, Wang J, Li T, Wu J, Wang J, Wen S, Huang J, Shi Y, Zheng K, Zhai Y, Li X. Hybrid capture-based sequencing enables highly sensitive zoonotic virus detection within the One Health framework. Pathogens. 2025;14(3):264.
  44. Feng Y, Ma J, Sun S, Chi L, Kou Z, Tu C. Epidemiology of animal rabies—China, 2010–2020. China CDC Weekly. 2021;3(39):815.
  45. Qureshi KA, Parvez A, Fahmy NA, Abdel Hady BH, Kumar S, Ganguly A, et al. Brucellosis: epidemiology, pathogenesis, diagnosis and treatment–a comprehensive review. Annals of Medicine. 2023;55(2):2295398.
  46. Erkyihun GA, Alemayehu MB. One Health approach for the control of zoonotic diseases. Zoonoses. 2022;2(1):963.
  47. Kheirallah KA, Al-Mistarehi AH, Alsawalha L, Hijazeen Z, Mahrous H, Sheikali S, et al. Prioritizing zoonotic diseases utilizing the One Health approach: Jordan's experience. One Health. 2021;13:100262.
  48. Ghai RR, Wallace RM, Kile JC, Shoemaker TR, Vieira AR, Negron ME, et al. A generalizable One Health framework for the control of zoonotic diseases. Scientific Reports. 2022;12(1):8588.
  49. McClymont H, Bambrick H, Si X, Vardoulakis S, Hu W. Future perspectives of emerging infectious diseases control: a One Health approach. One Health. 2022;14:100371.
  50. Dadar M, Tiwari R, Sharun K, Dhama K. Importance of brucellosis control programs of livestock on the improvement of One Health. The Veterinary Quarterly. 2021;41(1):137-151.
  51. Shi J, Zeng X, Cui P, Yan C, Chen H. Alarming situation of emerging H5 and H7 avian influenza and effective control strategies. Emerging Microbes & Infections. 2023;12(1):2155072.
  52. Rehman S, Rantam FA, Batool K, Shehzad A, Effendi MH, Witaningrum AM, et al. Emerging threats and vaccination strategies of H9N2 viruses in poultry in Indonesia: a review. F1000Research. 2022;11:548.
  53. Marrana M. Epidemiology of disease through the interactions between humans, domestic animals, and wildlife. In: One Health. Academic Press; 2022:73-111.
  54. Wouters OJ, Shadlen KC, Salcher-Konrad M, Pollard AJ, Larson HJ, Teerawattananon Y, et al. Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment. The Lancet. 2021;397(10278):1023-1034.
  55. Sturgis P, Brunton-Smith I, Jackson J. Trust in science, social consensus and vaccine confidence. Nature Human Behaviour. 2021;5(11):1528-1534.
  56. Rahman M, Adeli M, Schellhorn HE, Jithesh PV, Levy O. Precision vaccinology for infectious diseases. Frontiers in Immunology. 2024;15:1400443.
  57. Ong E, Wong MU, Huffman A, He Y. COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning. Frontiers in Immunology. 2020;11:1581.
  58. Charlton Hume HK, Vidigal J, Carrondo MJ, Middelberg AP, Roldão A, Lua LH. Synthetic biology for bioengineering virus‐like particle vaccines. Biotechnology and Bioengineering. 2019;116(4):919-935.
Archives of Razi Institute
Volume 80, Issue 3
May and June 2025
Pages 649-662

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