WORK EXPERIENCE AND APPOINTMENTS
RESEARCH INTERESTS
Host – Pathogen interactions in HIV and development of antivirals
Replication of all viruses depends to a large degree on specific host factors, from the recognition of specific cell surface receptors required for virus entry into a target cell to the packaging of cellular factors into virions. The molecular mechanism that dictate these interactions are poorly understood. My group is currently focussing on studying on identifying and characterizing novel antivirals against HIV and understanding the role of host proteins on HIV replication.
Basic Research:
On the basic front, our research contributions have advanced our basic understanding of the HIV assembly process and molecular mechanisms that underlie the interaction between the HIV viral infectivity protein (Vif) and the host cellular proteins belonging to the APOBEC3 family (A3G and A3F), which function as HIV host restriction factors (Virology 2018; J. General Virology, 2018; Virology, 2007; Retrovirology, 2007; Virology, 2008; J. Virol, 2009; PLoS One 2012).
Our research has demonstrated that in addition to its anti-HIV activity, human A3B protein has a dual role in developing multiple forms of cancer where it was found to be highly upregulated. The mechanism of upregulation of A3B in cancer was not known. Our group has identified a key cellular protein hnRNPA3 as an interacting partner of A3G, which may serve as a potential candidate for targeted intervention in cancer cells (J Cell Biochem, 2018).
We have also identified that an important cellular protein COX7A is involved in cellular proliferation in lung cancers. We have demonstrated that low levels of COX7A1 gene expression is essential to regulate cell viability and inhibit cell death in lung adenocarcinomas These results strongly suggest that the novel COX7A1 protein plays a crucial role in the etiology of lung adenocarcinoma and is a promising biomarker for analyzing lung cancer disease progression (BBRC 2017).
We have recently identified the important role of a specific potassium ions family in HIV entry (Scientific Reports 2019)
Applied/Translational Research:
On the applied front, our research has significantly advanced our understanding of a new class of HIV antivirals termed as Maturation Inhibitors, of which she had discovered the mechanism of action of a first-in-class maturation inhibitor Bevirimat (PNAS, 2003). We have further characterized these anti-HIV compounds on multiple worldwide HIV subtypes and substantiated them as promising candidates for their clinical development as anti-HIV therapeutics (Scientific Reports 2016; Scientific Reports 2017).
The first-in-class maturation inhibitor Bevirimat reached phase II clinical trials, but was ineffective against a certain group of HIV-1 subtype C viruses having Gag polymorphisms and that are highly prevalent in India and Africa. In key advancements, we have further identified novel Bevirimat analogs and other compounds with enhanced potency against all major HIV subtypes (Scientific Reports 2016; Scientific Reports 2017; Virology 2018).
My research group has further identified and characterized the mechanism of resistance obtained against maturation inhibitors (Journal of Virology, 2018). The Maturation Inhibitors developed by our team will add to the repertoire of drugs currently used for anti-HIV/AIDS HAART therapy. In this regard, we have established collaborations with industrial partners, DFH Pharma, Gaithersburg, Maryland, USA, Pfizer, USA and Hetero Drugs, Hyderabad, India and has plan to initiate clinical trials with the lead compounds in the near future.
In another major discovery, my group has identified and characterized the activity of Proteasome inhibitors as a novel class of HIV latency reversal agents, which can reactivate HIV and lead to production of non-infectious virus particle. Her group has elucidated the mechanism of action of these compounds and observed an important role of APOBEC proteins in production of non-infectious viruses (Journal of General Virology 2018).
In a collaborative work with Dr. Devashish Sengupta in Assam University, Silchar, we have elucidated the role of amphiphilic Zn(II) nitroporphyrin derivatives as HIV-1 entry inhibitors (European Journal of Medicinal Chemistry, 2019)
Academic Collaborations:
1. Ongoing Industry-Academia Collaboration with Hetero Research Foundation, Hyderabad to characterize the anti-viral activity of their lead compounds against HIV-1.
2.Ongoing Collaboration with DFH Pharma, USA since 2013 to screen potential anti-HIV compounds and also identifying the mechanism of action of these compounds against HIV subtype C. Our collaboration has resulted in several publications.
3.Ongoing Collaborations with Dr. Devashish Sen Gupta at Assam University, Silchar, to test the activity of Porphyrins and Fullerenes as anti-HIV agents. Our work has resulted in several publications and a patent.
Patent Obtained:
Co-inventor on patent (# 454199) granted on 25/09/2023 – Title- MESO-TRIS-CARBOXY PHENYL PORPHYRIN- FULLERENE ADDUCTS AS ANTI-HIV AGENTS.