Acta Scientific Microbiology (ISSN: 2581-3226)

Research Article Volume 5 Issue 2

Doxycycline and Ribavirin as Antiviral and Novel Combinational Drug to Treat Dengue, Chikungunya and as the Most Potent Antivirals for COVID-19

Rajarajan Swaminathan1*, Shanthi Sabarimurugan2, Sangeetha Kothandam3 and Indu Purushothaman4

1Professor, PG and Research, Department of Microbiology and Biotechnology Presidency College (Aut), University of Madras and Centre for Drug Design, Discovery and Development of Drug, SRM University, Haryana, New Delhi, India
2School of Biomedical Sciences, Faculty of Health and Biomedical Sciences, QE II Medical Centre Campus, The University of Western Australia, Perth, Australia
3Associate Lecturer, Bharath Institute of Higher Education and Research, Chennai, India
4PG and Research, Department of Microbiology and Biotechnology, Presidency College (Aut), University of Madras, India

*Corresponding Author:Rajarajan Swaminathan, Professor, PG and Research, Department of Microbiology and Biotechnology Presidency College (Aut), University of Madras and Centre for Drug Design, Discovery and Development of Drug, SRM University, Haryana, New Delhi, India.

Received: December 17, 2021; Published: January 27, 2022


Objectives: To discover an effective antiviral for the treatment of Dengue and Chikungunya by in-silico and in-vitro antiviral studies. To detect highly potent antiviral by in-silico evaluation to combat the unabated prevalence of COVID-19 as the second wave despite ongoing vaccination for emergency use.

Methods: The in-silico antiviral studies on Dengue and CHIKV have been studied through molecular docking and confirmed through in-vitro studies. The minimum nontoxic concentration of Doxycycline and Ribavirin were evaluated by cytotoxicity assay and the efficacy of monotherapy and combinational therapy was experimentally evaluated against CHIKV and Dengue serotypes in Vero cell lines. The statistical analysis was done through GraphPad Prism. Along with Doxycycline and Ribavirin, another five drugs have been studied the anti-COVID-19 effect through virtual screening. The 3D structure of the SARS-CoV-2 main protease protein was retrieved from PDB and docked with compounds using Auto Dock 4.2.

Results: In-silico docking efficacy of Doxycycline and Ribavirin were justified by the results of in-vitro antiviral assay as monotherapy on Dengue and CHIKV. Interestingly the combinational efficacy of Doxycycline/Ribavirin was slightly superior to the monotherapy MIC value. Interestingly the combinational effect of Doxycycline and Ribavirin exhibited superior synergetic inhibitory activity than individual drug efficacy. The com-binational antiviral efficacy as MIC against CHIKV strains were 62.5 and 125 µg/ml for Asian and ESCA strain respectively. The combinational MIC of Doxycycline and Ribavirin on Dengue subtypes 1, 3, and 4 were 7.8μg/ml, and Dengue 2 was 3.9μg/ml. All the statistical analyses were highly significant at P < 0.0001. Enthused by the results on Dengue and Chikungunya, the antiviral efficacy of these drugs to SARS-CoV-2 was studied by in-silico assay in comparison with Remdesivir, Hydroxychloroquine, Chloroquine, Azithromycin, and Favipiravir by their relative docking efficiency.

Conclusion: Doxycycline and Ribavirin are found to be potentially safe and efficacious for the treatment of Dengue/Chikungunya and the novel combination of them is slightly superior to its individual effect. Also, Doxycycline and Ribavirin are considered as the most potential drug for further evaluation in the treatment of COVID-19.

Keywords: SARS-CoV-2; Dengue; Chikungunya Virus; in-vitro Assay; in-silico Assay


  1. WHO: Coronavirus death report - WHO. In., 25-4-2020 edn (2020).
  2. Xu Z., et al. “Pathological findings of COVID-19 associated with acute respiratory distress syndrome”. Lancet Respiratory Medicine 4 (2020): 420-422.
  3. Kozlov M. “Merck’s COVID pill loses its lustre: what that means for the pandemic”. In: Nature 13 (2021).
  4. Maheswari S., et al. “Air pollution enhances susceptibility to novel coronavirus (COVID-19) infection - an impact study”. Environmental Analysis Health and Toxicology 4 (2020): e2020020-2020020.
  5. Haagmans BL and Osterhaus AD. “Coronaviruses and their therapy”. Antiviral Research 2-3 (2006): 397-403.
  6. Fehr AR and Perlman S. “Coronaviruses: an overview of their replication and pathogenesis”. Methods in Molecular Biology 1282 (2015): 1-23.
  7. Sabarimurugan S., et al. “Comprehensive review on the prevailing COVID-19 therapeutics and the potential of repurposing SARS-CoV-1 candidate drugs to target SARS-CoV-2 as a fast-track treatment and prevention option”. Annals of Translational Medicine's 19 (2020): 1247.
  8. Stroher U., et al. “Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha”. Journal of Infectious Diseases 7 (2014): 1164-1167.
  9. Morgenstern B., et al. “Ribavirin and interferon-beta synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines”. Biochemical and Biophysical Research Communications 4 (2005): 905-908.
  10. Ferron F., et al. “Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA”. Proceedings of the National Academy of Sciences of the United States of America 2 (2018): E162.
  11. Castro JE., et al. “Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever”. Clinical and Developmental Immunology 2011 (2011): 370872.
  12. Rothan HA., et al. “Inhibitory effect of doxycycline against dengue virus replication in vitro”. Archives of Virology4 (2014): 711-718.
  13. Menzel M., et al. “Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients”. Scientific Report 6 (2016): 28698-28698.
  14. Colson P., et al. “Chloroquine for the 2019 novel coronavirus SARS-CoV-2”. International Journal of Antimicrobial Agents 3 (2020): 105923.
  15. Sabarimurugan S., et al. “Computational screening of dual inhibitors from FDA approved antiviral drugs on SARS-CoV-2 spike protein and the main protease using molecular docking approach”. Acta Virology2 (2021): 160-172.
  16. Zhang L., et al. “Alpha-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment”. Journal of Medicinal Chemistry (2020).
  17. Rothan HA., et al. “A combination of doxycycline and ribavirin alleviated chikungunya infection”. PLoS One 5 (2015): e0126360.
  18. Franco EJ., et al. “The effectiveness of antiviral agents with broad-spectrum activity against chikungunya virus varies between host cell lines”. Antiviral Chemistry and Chemotherapy 26 (2018): 2040206618807580.
  19. Di Caprio R., et al. “Anti-Inflammatory Properties of Low and High Doxycycline Doses: An <i>In Vitro</i> Study”. Mediators of Inflammation 2015 (2015): 329418.
  20. Kandeel M and Al-Nazawi M. “Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease”. Life Science 251 (2020): 117627.
  21. Elfiky AA. “Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study”. Life Science (2020): 117592.
  22. Tian X., et al. “Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody”. Emerging Microbes and Infections 1 (2020): 382-385.
  23. de Wit E., et al. “Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection”. Proceedings of the National Academy of Sciences of the United States of America 12 (2020): 6771.
  24. Cai Q., et al. “Experimental treatment with favipiravir for COVID-19: an open-label control study”. Engineering (2020).
  25. Wang M., et al. “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro”. Cell Research3 (2020): 269-271.
  26. FDA: Hydroxychloroquine (2020).
  27. Ulhaq ZS and Soraya GV. “Interleukin-6 as a potential biomarker of COVID-19 progression”. Medecine et Maladies Infectiousness 4 (2020): 382-383.
  28. Wang W-K., et al. “Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome”. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America7 (2004): 1071-1075.
  29. Ikeda-Dantsuji Y., et al. “Effects of levofloxacin and doxycycline on interleukin-6 production of Chlamydia trachomatis-infected human synovial fibroblasts”. Chemotherapy 5 (2007): 332-337.
  30. M Fredeking T., et al. “Dengue patients treated with doxycycline showed lower mortality associated to a reduction in IL-6 and TNF levels”. Recent Patents on Anti-infective Drug Discovery1 (2015): 51-58.


Citation: Rajarajan Swaminathan., et al. “Doxycycline and Ribavirin as Antiviral and Novel Combinational Drug to Treat Dengue, Chikungunya and as the Most Potent Antivirals for COVID-19". Acta Scientific Microbiology 5.2 (2022): 69-81.


Copyright: © 2022 Rajarajan Swaminathan., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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