A group of researchers of the University of Kerala have found potential in a combination of antiretroviral HIV drugs ritonavir and atazanavir in treating COVID-19.
A study led by the Department of Computational Biology and Bioinformatics based on molecular docking and dynamics studies highlighted the promise held by drug combination as a remedy for the disease. The university is set to submit the findings to the Indian Council of Medical Research (ICMR) for further studies.
The findings of the study undertaken by Abhinand C.S., Perumana R. Sudhakaran, Oommen V. Oommen and department head Achuthsankar S. Nair in collaboration with Anand Krishnamurthy, senior technical manager, Dassault Systèmes, Chennai, has been published in the Journal of Biomolecular Structure and Dynamics.
The results of the study suggested that ritonavir, a protease inhibitor, can target both viral 3CL protease and host protein TMPRSS2, while atazanavir inhibits human protein Cathepsin L which is involved in virus fusion and transport in endosomes.
The researchers examined the feasibility of repurposing the existing antiviral protease inhibitor drugs that are used to treat COVID-19. The structural characteristics of proteolytic components of SARS-CoV-2, particularly its main protease and the S-protein, were analysed.
This was intended to examine whether the presently available antiviral drugs that target the proteases of other virus, especially coronavirus-mediated infection can be repurposed against SARS-CoV-2 using molecular docking and dynamics studies. While the main objective of the endeavour was to identify molecule (or molecules) that can target the proteolytic process during both the initial entry phase and intracellular events, the results showed that protease inhibitors particularly ritonavir either alone or in combination with drugs such as atazanavir have the potential to treat the disease.
Dr. Achuthsankar said the drug combinations could be used on COVID-19 patients without any hurdles since the FDA-approved drugs, which have completed clinical tests and safety assessments, were employed for drug repurposing. However, further pharmacokinetic analysis would be required to fix the relative dose to obtain an optimal effect to achieve an effective reduction in viral load.
