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.
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
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