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  1. E-pharmacophore based virtual screening of potent lead molecules against Cystic Fibrosis: An in silico study
    Jeyaraman S, Sankar J, Wong LS, Muthusamy K
    Comput Biol Chem, 2024 Dec;113:108249.
    PMID: 39427605 DOI: 10.1016/j.compbiolchem.2024.108249
    Cystic fibrosis is an autosomal recessive condition caused by mutations in the CFTR gene, which encodes the CFTR protein. Currently, CF is a life-limiting illness that has a limited cure. The present study aimed to identify top leads against CFTR protein with F508del in comparison with Lumacaftor. In this study, a homology model of the NBD domain of CFTR protein was developed using the available NBD domain crystal structure. The protein model was refined through apo dynamics. Energy-optimized pharmacophore mapping was carried out to identify essential features for CFTR, resulting in a model with a hydrogen-bond donor, two hydrogen-bond acceptors, and three aromatic ring sites. A screening of a compound from the NPASS database using these DAARRR six-point-pharmacophore features led to the identification of potential ligands that could act against CFTR protein. Further studies such as ADME/T, molecular dynamics, MM_GBSA, and DFT were performed to identify the top-hit compound from the NPASS database. The compound Anguibactin (NPC41982) has been identified as a top lead that exhibits higher binding affinity and stability than the reference compound Lumacaftor, suggesting their potential to bind to the active site of the CFTR protein. These compounds could serve as starting points for the development of drug-like molecules for treating cystic fibrosis.
  2. Cross-Section of Hypertensive Molecular Signaling Pathways: Understanding Pathogenesis and Identifying Improved Drug Targets
    Sankar J, Rajendran K, Wong LS, Muthusamy K
    Curr Hypertens Rev, 2025 Jan 20.
    PMID: 39838689 DOI: 10.2174/0115734021342501250107052350
    INTRODUCTION: Hypertension is a chronic medical state and a major determining factor for cardiovascular and renal diseases. Both genetic and non-genetic factors contribute to hypertensive conditions among individuals. The renin-angiotensin-aldosterone system (RAAS) is a major genetic target for the anti-hypertension approach.

    PURPOSE OF THE STUDY: The majority of classical antihypertensive drugs were mainly focused on the RAAS signaling pathways. Though these antihypertensive drugs control blood pressure (BP), they have mild to severe life-threatening effects. Unrevealing effective hypertensive targets for BP management is essential. The effective targets could emerge either from RAAS-dependent or RAAS-independent pathways and/or through the cross-talks among them.

    RESULTS: Analyzing the physiopathological mechanisms of hypertension has the benefit of understanding the interactions between these systems which helps in better understanding of drug targets and the importance of emergence of novel therapeutics.

    CONCLUSION: This review is about the signaling pathways involved in hypertension pathogenesis and their cross-talks and it contributes to a better understanding of the etiology of hypertension.

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