Major Research Focus

• Novel Antivirals (Both virus- and host-based approaches)

• G Protein-Coupled Receptor (GPCR) modulators

• Organic Chemistry methodology development and Medicinal Chemistry for bioactive molecules

Novel Antivirals (Virus- and Host-Targeted Strategies)

The recent COVID-19 pandemic caused by SARS-CoV-2 underscored the urgent need for broad-spectrum antivirals to better prepare for future viral outbreaks. Several pathogens—including Pneumoviridae (RSV), Zika virus, Filoviridae (Ebola), Orthomyxoviridae (Influenza), Togaviridae (Chikungunya), Poxviridae (monkeypox), and Flaviviridae (Dengue virus)—already circulate in human populations and can cause illnesses ranging from mild to severe, with significant potential to spark new epidemics. For many of these viruses, effective vaccines or antiviral treatments are lacking, and existing options face challenges such as limited efficacy, safety concerns, vaccine hesitancy, or the emergence of resistance. Even though the acute phase of the SARS-CoV-2 pandemic has passed, the threat remains that another zoonotic coronavirus could cross into humans and trigger a SARS-CoV-3 outbreak.

Our goal is to develop broad-spectrum antiviral agents targeting emerging zoonotic viruses—including Dengue, Zika, Ebola, Respiratory Syncytial Virus, coronaviruses, and Influenza—where there is a clear unmet need for effective therapeutics.

Our strategy involves two complementary approaches. First, we are designing direct-acting antivirals that inhibit essential viral proteins across different stages of the viral life cycle. At the same time, we are exploring host-targeted interventions that modulate cellular factors involved in viral replication and immune responses. This approach is particularly important because, in many severe infections, excessive immune activation—such as cytokine storms—can cause more damage than the virus itself. Targeting host factors offers two key benefits over direct-acting antivirals (DAAs): (1) disrupting fundamental cellular pathways used by multiple viruses may yield broad-spectrum activity, and (2) host proteins are genetically stable, dramatically reducing the likelihood of drug-resistant variants.

G Protein-Coupled Receptor (GPCR) Modulators

G Protein-Coupled Receptors (GPCRs) represent the largest and most diverse family of cell membrane receptors in the human genome. What sets them apart is their distinctive seven-transmembrane (7TM) helical structure. With over 800 genes in total, including 400 olfactory receptors, GPCRs play a critical role in transmitting a wide range of chemical and physical signals. These include signals from proteins, peptides, neurotransmitters, hormones, lipids, organic compounds, sugars, and even light. Consequently, GPCRs are essential for many physiological processes, including the regulation of behaviour, mood, blood pressure, cognition, taste, smell, immune response, hormonal balance, kidney function, and even the development and progression of cancer. Due to their central role in cell signaling, GPCRs are vital drug targets. These receptors have significant pharmacological importance and are a major focus of drug development and academic and pharmaceutical research. GPCRs are involved in approximately 34% of all FDA-approved drugs and account for approximately 27% of the global therapeutic market. Between 2011 and 2015, the combined sales of GPCR-targeting drugs were estimated at US$890 billion.

Orphan GPCRs; Despite over four decades of research on GPCRs as drug targets, their diverse structures and functions continue to offer new possibilities for therapeutic development. The sequencing of the human genome and advances in bioinformatics have led to the identification of about 800 genes encoding GPCRs. Among these, over 100 receptors (excluding olfactory receptors, which are mostly orphaned) are currently considered "orphan GPCRs," meaning their endogenous ligands remain unknown. These orphan receptors are believed to play vital roles in key cellular processes such as neurotransmission, growth, differentiation, secretion, and migration, yet their precise functions are still unclear due to the lack of identified binding partners. As such, discovering new ligands to modulate these orphan GPCRs is critical for uncovering their roles in both normal physiology and disease.

Our research primarily focuses on the development of modulators—both agonists and antagonists—for a variety of GPCRs, with particular attention given to orphan GPCRs involved in inflammatory, cancer, metabolic, and neurodegenerative diseases. We employ a range of methodologies, including computational techniques like virtual screening, modeling, docking, and simulations, as well as hit-to-lead strategies that involve comprehensive structure-activity relationship (SAR) studies. These approaches are followed by medicinal chemistry optimization to refine compounds and progress them toward preclinical testing.