We are glad to announce that Ramakrishna Mission Vivekananda Educational and Research Institute (RKMVERI) will be conducting a special colloquium on “Emerging and Re-emerging Viral Diseases: Host Immunity and Therapeutic Interventions” on 01 Mar 2024, 12 noon at Seminar Hall, Narendrapur Campus.

Speaker : Dr.  Anirban Basu, NBRC, Gurugram
Co-ordinator: Prof. Abhijit Chakrabarti

Abstract

Development of a new drug being a high-risk, time consuming and very laborious process, repositioning/repurposing of drugs has been the focus of many groups working in the field of drug discovery. Drug repositioning (DR) aims to find new uses of existing safe drugs in different disease settings. Not only in the developed nations has this approach revolutionized drug discovery, many developing countries are also currently focusing on the same strategy thus seeking for an alternative to high costs and failure rates associated with the drug discovery pipeline. Traditional drug development strategy consists of five steps, i.e. 1) discovery and preclinical studies, 2) review of its safety, 3) Clinical research, 4) FDA review, 5) assessment of post-marketing safety by FDA. On the other hand, repositioning of drug entails four steps: 1) compound identification, 2) Retrieval of the same, 3) development, 4) FDA post-market safety monitoring, thus cutting off a significant cost and time when compared to traditional drug development. Reports suggest that while repositioning strategy for a drug development costs around 1.2 billion dollars, nearly about 16 billion dollars is being demanded by the traditional approach. Use of drugs such as sildenafil, bupropion & thalidomide for erectile dysfunction, smoking cessation, and multiple myeloma respectively also represents the high rewarding nature of the repositioning approach at a very low cost thus warranting further research in the same line of study. Absence of safe, efficient as well as cost effective vaccine and anti-viral drug prompts us to explore the potential of known drug as a therapeutic strategy for Japanese Encephalitis Virus (JEV) infection. By exploring the pathways which are involved in inflammation, we have identified Minocycline, which is an approved drug with a long standing record of acceptable safety and has a similar spectrum to Doxycycline, as a potential therapeutic candidate against JEV infection. Based upon pre-clinical study undertaken in our laboratory at National Brain Research Centre, a Phase III clinical trial has been completed at King George Medical University (KGMU), Lucknow, where minocycline has been used as a therapy for JE patients and the patients with Acute Encephalitis Syndrome (AES). Results of the trial indicates a potential benefit that Minocycline confers upon patients, especially in those who survive the initial days in hospital. These findings could form the basis for planning a larger study and possibly including minocycline in the management of AES and JE. Recently we have explored the efficacy of atorvastatin (AT) calcium trihydrate in JEV & CHPV (Chandipura Virus)-infected mice models. AT calcium trihydrate is a well-established statin drug that is being prescribed by medical practitioners against hypercholesterolemia. Apart from its established role, AT has been implicated as an anti-oxidative and anti-neurodegenerative agent. AT being able to cross the blood brain barrier (BBB) demonstrates promising results in our preliminary studies, providing resistance to viral replication and enhancing the survival of the virus-infected animals. At present we are conducting studies regarding molecular mechanisms by which AT imparts its role in the context of JEV and CHPV infections. More recently, we have shown the therapeutic potential of AMG487, an antagonist of CXCR3, in Dengue virus (DV) as well as in JEV infection. We have reported the crucial role platelet cytokine PF4 plays in enhancing replication and propagation of both DV and JEV in host cells including monocytes by inhibiting IFN response of these immune cells. Definitely the PF4-CXCR3-IFN axis acts as a potential target for developing treatment regimens against viruses including DV and JEV.