Hydroxychloroquine and Azithromycin in Treating Emerging Viral Infections: Efficacy, Safety, and Mechanisms in Monkeypox and Influenza A (H5N1)
- Department of Microbiology, Skyline University, Nigeria
- Department of Biochemistry, Skyline University, Nigeria
- Ministry of National Guard Hospital, Saudi Arabia
- Department of Medicinal Research, Kaohsiung Medical University Hospital, Taiwan
- Department of Public Health, Obafemi Awolowo University, Ile-Ife, Nigeria
- Received
- Published
Abstract
Due to their antiviral and immunomodulatory properties, hydroxychloroquine and azithromycin have gained attention as potential treatments for emerging viral infections, including monkeypox and Influenza A. Hydroxychloroquine has demonstrated in vitro efficacy in inhibiting viral replication, while azithromycin is primarily used as an antibiotic but has shown some promise in modulating inflammation and treating secondary infections. However, clinical evidence supporting the use of these drugs for emerging infections remains inconclusive, with existing studies often yielding mixed results. The lack of large-scale randomized controlled trials (RCTs) and long-term safety data further complicates their use in treating novel viral pathogens. This review highlights the need for comprehensive clinical trials to assess the efficacy, safety, and mechanisms of action of hydroxychloroquine and azithromycin in the treatment of emerging infections. Furthermore, it emphasizes the importance of long-term monitoring to better understand the adverse effects and the potential benefits of these drugs, particularly in high-risk populations. Future research should focus on combination therapy studies and comparative trials with other antiviral treatments to establish more effective therapeutic strategies for new viral threats.
References
- 1. Sah, R., Padhi, B. K., Siddiq, A., Abdelaal, A., Reda, A., Ismail Lashin, B., & Rodriguez-Morales, A. J. (2022) A public health emergency of international concern was declared by the World Health Organization for monkeypox. Global Security: Health, Science and Policy, 7(1), 51-56.
- 2. Ejaz, H., Junaid, K., Younas, S., Abdalla, A. E., Bukhari, S. N. A., Abosalif, K. O., ... & Anwar, N. (2022). Emergence and dissemination of monkeypox, an intimidating global public health problem. Journal of infection and public health, 15(10), 1156-1165.
- 3. Lai, S., Qin, Y., Cowling, B. J., Ren, X., Wardrop, N. A., Gilbert, M., & Yu, H. (2016). Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997–2015: a systematic review of individual case data. The Lancet Infectious Diseases, 16(7), e108-e118.
- 4. Shao, W., Li, X., Goraya, M. U., Wang, S., & Chen, J. L. (2017). Evolution of influenza a virus by mutation and re-assortment. International journal of molecular sciences, 18(8), 1650.
- 5. Saghir, S. A., AlGabri, N. A., Alagawany, M. M., Attia, Y. A., Alyileili, S. R., Elnesr, S. S., & Abd El-Hack, M. E. (2021). Chloroquine and hydroxychloroquine for preventing and treating COVID-19: A fiction, hope or hype? An updated review. Therapeutics and clinical risk management, 371-387.
- 6. Abdulsalam, M., Salihu, A. T., Usman, H. Y., & Usman, M. Y. (2024). Protein Biosynthesis in Microorganisms: Mechanisms, Regulation, and Biotechnological Applications. World Journal of Advanced Research and Reviews, 21(1), 869-881.
- 7. Oliver, M. E., & Hinks, T. S. (2021). Azithromycin in viral infections. Reviews in medical virology, 31(2), e2163.
- 8. Venditto, V. J., Haydar, D., Abdel-Latif, A., Gensel, J. C., Anstead, M. I., Pitts, M. G., & Feola, D. J. (2021). Immunomodulatory effects of azithromycin revisited: potential applications to COVID-19—frontiers in immunology, 12, 574425.
- 9. Ulrich, H., Pillat, M. M., & Tárnok, A. (2020). Dengue fever, COVID‐19 (SARS‐CoV‐2), and antibody‐dependent enhancement (ADE): a perspective. Cytometry Part A, 97(7), 662-667.
- 10. Saheed, Y. K., Salau-Ibrahim, T. T., Abdulsalam, M., Adeniji, I. A., & Balogun, B. F. (2024). Modified bi-directional long short-term memory and hyperparameter tuning of supervised machine learning models for cardiovascular heart disease prediction in the mobile cloud environment. Biomedical Signal Processing and Control, 94, 106319.
- 11. Alijotas-Reig, J., Esteve-Valverde, E., Belizna, C., Selva-O'Callaghan, A., Pardos-Gea, J., Quintana, A., & Miró-Mur, F. (2020). Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review. Autoimmunity reviews, 19(7), 102569.
- 12. Zhou, Y. W., Xie, Y., Tang, L. S., Pu, D., Zhu, Y. J., Liu, J. Y., & Ma, X. L. (2021). Therapeutic targets and interventional strategies in COVID-19: mechanisms and clinical studies. Signal transduction and targeted therapy, 6(1), 317.
- 13. Kroschinsky, F., Stölzel, F., von Bonin, S., Beutel, G., Kochanek, M., Kiehl, M., & Intensive Care in Hematological and Oncological Patients (iCHOP) Collaborative Group. (2017). New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. Critical Care, 21, 1-11.
- 14. Firth, A., & Prathapan, P. (2020). Azithromycin: the first broad-spectrum therapeutic. European journal of medicinal chemistry, 207, 112739.
- 15. Abdulsalam, M., Fatima, Z. Y.U., Hasiya, U. A., Ummulkhuthum, A. T., Aisha, W. N., Muhammad, F. Y. (2024). Deciphering the Genetic Code: Mechanisms, Evolution, and Implications for Biotechnology. World Journal of Advanced Research and Review. 21(1):858-868.
- 16. Oliver, M. E., & Hinks, T. S. (2021). Azithromycin in viral infections. Reviews in medical virology, 31(2), e2163.
- 17. Abdulsalam, M. (2024). Exploring the Therapeutic Promise of Cationic Antibacterial Peptides. Biological Sciences, 4(3), 692-700.
- 18. Shayo, A., Buza, J., & Ishengoma, D. S. (2015). Monitoring of efficacy and safety of artemisinin-based antimalarials for treatment of uncomplicated malaria: a review of evidence of implementation of anti-malarial therapeutic efficacy trials in Tanzania. Malaria journal, 14, 1-12.
- 19. Devaux, C. A., Rolain, J. M., Colson, P., & Raoult, D. (2020). New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? International journal of antimicrobial agents, 55(5), 105938.
- 20. Abdulsalam, M., Hamisu, A. A., Ahmad, A. M., Wakili, F. B., Annu, F. S., & Garba, M. M. (2024). Microbiome Dynamics and Strategic Management Strategies: Exploring Synergies between Integrative Medicine Modalities and Microbial Balance. Biological Sciences, 4(3), 725-735.
- 21. Zhao, Y., Zhang, J., Zheng, K., Thai, S., Simpson Jr, R. J., Kinlaw, A. C., & Wang, T. (2022). Serious cardiovascular adverse events associated with hydroxychloroquine/chloroquine alone or with azithromycin in patients with COVID-19: a pharmacovigilance analysis of the FDA adverse event reporting system (FAERS). Drugs-Real World Outcomes, 9(2), 231-241.
- 22. RECOVERY Collaborative Group. (2020). Effect of hydroxychloroquine in hospitalized patients with COVID-19. New England Journal of Medicine, 383(21), 2030-2040.
- 23. Wright, M., & Piedimonte, G. (2011). Respiratory syncytial virus prevention and therapy: past, present, and future. Pediatric pulmonology, 46(4), 324-347.
- 24. Slim, M. A., Turgman, O., van Vught, L. A., van der Poll, T., & Wiersinga, W. J. (2024). Non-conventional immunomodulation in the management of sepsis. European Journal of Internal Medicine, 121, 9-16.
- 25. Abdulsalam, M., Musa, I. O., Livinus, M. U., Elelu, S. A., Ibrahim, G. O., Salami, O. L., & Pal, S. K. (2024). Blue Bioeconomy and Biomedical Innovation. In Marine Bioprospecting for Sustainable Blue-bioeconomy (pp. 143-157). Cham: Springer Nature Switzerland.
- 26. Doyno, C., Sobieraj, D. M., & Baker, W. L. (2021). Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose. Clinical Toxicology, 59(1), 12-23.
- 27. Maza, A., Montaudié, H., Sbidian, E., Gallini, A., Aractingi, S., Aubin, F., & Paul, C. (2011). Oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non‐plaque psoriasis. Journal of the European Academy of Dermatology and Venereology, 25, 19-27.
- 28. Offerhaus, J. A., Wilde, A. A., & Remme, C. A. (2020). Prophylactic (hydroxy) chloroquine in COVID-19: potential relevance for cardiac arrhythmia risk. Heart Rhythm, 17(9), 1480-1486.
- 29. Boussios, S., Pentheroudakis, G., Katsanos, K., & Pavlidis, N. (2012). Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management. Annals of Gastroenterology, 25(2), 106.
- 30. Musa, I. O., Isibor, P. O., Samuel, J. O., Mustapha, A., Mustapha, A., Akande, S., ... & Adeniji, H. (2024). Introduction to Nanotoxicology. In Environmental Nanotoxicology: Combatting the Minute Contaminants (pp. 1-22). Cham: Springer Nature Switzerland.
- 31. Mascolo, A., Berrino, P. M., Gareri, P., Castagna, A., Capuano, A., Manzo, C., & Berrino, L. (2018). Neuropsychiatric clinical manifestations in elderly patients treated with hydroxychloroquine: a review article. Inflammopharmacology, 26(5), 1141-1149.
- 32. MulLer, R. (2021). Systemic toxicity of chloroquine and hydroxychloroquine: prevalence, mechanisms, risk factors, prognostic and screening possibilities. Rheumatology International, 41(7), 1189-1202.
- 33. Zequn, Z., Yujia, W., Dingding, Q., & Jiangfang, L. (2021). Off-label use of chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir in COVID-19 risks prolonging the QT interval by targeting the hERG channel. European Journal of Pharmacology, 893, 173813.
- 34. Soar, J., Perkins, G. D., Abbas, G., Alfonzo, A., Barelli, A., Bierens, J. J., ... & Nolan, J. P. (2010). European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances: electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution. Resuscitation, 81(10), 1400-1433.
- 35. Parnham, M. J., Haber, V. E., Giamarellos-Bourboulis, E. J., Perletti, G., Verleden, G. M., & Vos, R. (2014). Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacology & therapeutics, 143(2), 225-245.
- 36. Grajales, D. B., & Kar, S. (2023). Exploring Monkeypox: Prospects for therapeutics through computational-aided drug discovery. Molecular Diversity, 1-25.
- 37. Imran, M., Alshammari, M. K., Arora, M. K., Dubey, A. K., Das, S. S., Kamal, M., ... & Dzinamarira, T. (2023). Oral brincidofovir therapy for monkeypox outbreak: a focused review on the therapeutic potential, clinical studies, patent literature, and prospects. Biomedicines, 11(2), 278.
- 38. Kumari, R., Sharma, S. D., Kumar, A., Ende, Z., Mishina, M., Wang, Y., & Sambhara, S. (2023). Antiviral approaches against influenza virus. Clinical microbiology reviews, 36(1), e00040-22.
- 39. Smyk, J. M., & Majewska, A. (2022). Favipiravir in the battle with respiratory viruses. Mini-Reviews in Medicinal Chemistry, 22(17), 2224-2236.
- 40. Rehman, S. U., Rehman, S. U., & Yoo, H. H. (2021). COVID-19 challenges and its therapeutics. Biomedicine & Pharmacotherapy, 142, 112015.
- 41. Carter, M. J. (2007). A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. Journal of Medical Microbiology, 56(7), 875-883.
- 42. Echeverría-Esnal, D., Martin-Ontiyuelo, C., Navarrete-Rouco, M. E., De-Antonio Cuscó, M., Ferrández, O., Horcajada, J. P., & Grau, S. (2021). Azithromycin in the treatment of COVID-19: a review. Expert review of anti-infective therapy, 19(2), 147-163.
- 43. Saheed, Y. K., Balogun, B. F., Odunayo, B. J., & Abdulsalam, M. (2023). Microarray gene expression data classification via Wilcoxon sign rank sum and novel Grey Wolf optimized ensemble-learning models. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 20(6), 3575-3587.
- 44. Bekheit, M. S., Panda, S. S., & Girgis, A. S. (2023). Potential RNA-dependent RNA polymerase (RdRp) inhibitors as prospective drug candidates for SARS-CoV-2. European Journal of Medicinal Chemistry, 252, 115292.
- 45. Gulati, P., Chadha, J., Harjai, K., & Singh, S. (2023). Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation. Frontiers in Microbiology, 13, 1073419.
- 46. Lane, J. C., Weaver, J., Kostka, K., Duarte-Salles, T., Abraham, M. T. F., Alghoul, H., ... & Prieto-Alhambra, D. (2020). Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study. MedRxiv.
- 47. Cooper, S. A., Desjardins, P. J., Turk, D. C., Dworkin, R. H., Katz, N. P., Kehlet, H., ... & Wu, C. (2016). Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. Pain, 157(2), 288-301.
- 48. Taylor, S. L., Leong, L. E., Mobegi, F. M., Choo, J. M., Wesselingh, S., Yang, I. A., ... & Simpson, J. L. (2019). Long-term azithromycin reduces Haemophilus influenzae and increases antibiotic resistance in severe asthma. American journal of respiratory and critical care medicine, 200(3), 309-317.
- 49. Hooks, M., Bart, B., Vardeny, O., Westanmo, A., & Adabag, S. (2020). Effects of hydroxychloroquine treatment on QT interval. Heart rhythm, 17(11), 1930-1935.
- 50. Chen, N., Zhang, B., Deng, L., Liang, B., & Ping, J. (2022). Virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2. Emerging microbes & infections, 11(1), 1371-1389.y
- 51. Mishra, A., Kaur, I., Sharma, A., Manu, M., De, U. K., Kumar, N., & Malik, Y. S. (2024). Antivirals: Approaches and the Way Forward. In Advances in Antiviral Research (pp. 1-40). Singapore: Springer Nature Singapore.
- 52. Skvortsov, T., & Maillard, J. Y. (2023). Viruses and Other Acellular Infectious Agents: Characteristics and Control. Hugo and Russell's Pharmaceutical Microbiology.
- 53. Matzke, G. R., Aronoff, G. R., Atkinson Jr, A. J., Bennett, W. M., Decker, B. S., Eckardt, K. U., ... & Murray, P. (2011). Drug dosing consideration in patients with acute and chronic kidney disease—a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International, 80(11), 1122-1137.
- 54. Zagaliotis, P., Petrou, A., Mystridis, G. A., Geronikaki, A., Vizirianakis, I. S., & Walsh, T. J. (2022). Developing New Treatments for COVID-19 through Dual-Action Antiviral/Anti-Inflammatory Small Molecules and Physiologically Based Pharmacokinetic Modeling. International Journal of Molecular Sciences, 23(14), 8006.
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