Research Title: Prospective Role of Peptide-Based Antiviral Therapy Against the Main Protease of SARS-CoV-2

Author: Balakumar Chandrasekarn, Published Year: 2021

Frontiers in Molecular Biosciences, 8

Faculty: Pharmacy

Abstract: The recently emerged coronavirus (SARS-CoV-2) has created a crisis in world health, and economic sectors as an effective treatment or vaccine candidates are still developing. Besides, negative results in clinical trials and effective cheap solution against this deadly virus have brought new challenges. The viral protein, the main protease from SARS-CoV-2, can be effectively targeted due to its viral replication and pathogenesis role. In this study, we have enlisted 88 peptides from the AVPdb database. The peptide molecules were modeled to carry out the docking interactions. The four peptides molecules, P14, P39, P41, and P74, had more binding energy than the rest of the peptides in multiple docking programs. Interestingly, the active points of the main protease from SARS-CoV-2, Cys145, Leu141, Ser139, Phe140, Leu167, and Gln189, showed nonbonded interaction with the peptide molecules. The molecular dynamics simulation study was carried out for 200 ns to find out the docked complex’s stability where their stability index was proved to be positive compared to the apo and control complex. Our computational works based on peptide molecules may aid the future development of therapeutic options against SARS-CoV-2.

Keywords: Peptide-Based Antiviral Therapy; Protease; SARS-CoV-2

Research Title: In silico Screening of Natural Phytocompounds Towards Identification of Potential Lead Compounds to Treat COVID-19

Author: Balakumar Chandrasekarn, Published Year: 2021

Frontiers in Molecular Biosciences, 8

Faculty: Pharmacy

Abstract: COVID-19 is one of the members of the coronavirus family that can easily assail humans. As of now, 10 million people are infected and above two million people have died from COVID-19 globally. Over the past year, several researchers have made essential advances in discovering potential drugs. Up to now, no efficient drugs are available on the market. The present study aims to identify the potent phytocompounds from different medicinal plants (Zingiber officinale, Cuminum cyminum, Piper nigrum, Curcuma longa, and Allium sativum). In total, 227 phytocompounds were identified and screened against the proteins S-ACE2 and Mpro through structure-based virtual screening approaches. Based on the binding affinity score, 30 active phytocompounds were selected. Amongst, the binding affinity for beta-sitosterol and beta-elemene against S-ACE2 showed −12.0 and −10.9 kcal/mol, respectively. Meanwhile, the binding affinity for beta-sitosterol and beta-chlorogenin against Mpro was found to be −9.7 and −8.4 kcal/mol, respectively. Further, the selected compounds proceeded with molecular dynamics simulation, prime MM-GBSA analysis, and ADME/T property checks to understand the stability, interaction, conformational changes, binding free energy, and pharmaceutical relevant parameters. Moreover, the hotspot residues such as Lys31 and Lys353 for S-ACE2 and catalytic dyad His41 and Cys145 for Mpro were actively involved in the inhibition of viral entry. From the in silico analyses, we anticipate that this work could be valuable to ongoing novel drug discovery with potential treatment for COVID-19.

Keywords: n silico Screening; Natural Phytocompounds; Lead Compounds; COVID-19

Research Title: Recent targeted discovery of phytomedicines to manage endocrine disorder develops due to adapting sedentary lifestyle

Author: Balakumar Chandrasekarn, Published Year: 2023

Faculty: Pharmacy

Abstract: The endocrine system is a series of glands that produce and secrete hormones that the body uses for a wide range of functions. These control many different bodily functions

Keywords: Recent targeted discovery of phytomedicines

Research Title: Biosynthetic exosome nanoparticles isolation, characterization, and their diagnostic and therapeutic applications

Author: Balakumar Chandrasekarn, Published Year: 2021

Faculty: Pharmacy

Abstract: Exosomes are of emerging interest in diverse pathological conditions due to their key role in cellular physiology. These entities can signal and change the phenotype of target cells and hence they have quantitative and qualitative impacts on disease. Exosomes are organically found nanoparticles released endogenously by the cellular structure of mammals. Due to limitations like instability in donor cells, lower production, and incapability to target the required cells, exosomes are not utilized clinically

Keywords: Exosome; nanoparticles; isolation; characterization

Research Title: An insight of protein structure predictions using homology modelling

Author: Balakumar Chandrasekarn, Published Year: 2021

Faculty: Pharmacy

Abstract: If the query sequence has similar with template structure, then the model structure can be easily predicted with high resolution. The homology modeling for structural prediction plays a crucial role to discover the novel drug target against the various diseases. Based on the two important principles such as laws of physics and evolution, the 3D protein structure can be predicted. According to the physical and evaluation principles, protein folds have stable and well-formed structure via minimizing the energy and protein molecule has outcome of gradual changes in sequence and structure. The homology modeling has different multi steps which are most accurate to predict the absolute model structure. When the sequence identity is below 15%, it cannot be used for further structure modeling which could be lead to deceptive conclusion. The maximum similarity between 30% and 40% obtained from the query and template sequences can be considered for further homology modeling. If the similarity is above 50%, then the obtained model is adequate quality which can be used for further molecular docking for protein-protein docking, protein-ligand complexes, and molecular dynamic simulation studies. This modeling technique is very comfortable, faster, and cost-effective. This chapter will discuss the different homology model for the prediction of protein structure for the drug development process

Keywords: Homology modeling; methods and tools used for homology modeling

Research Title: Bioinformatics in cancer detection

Author: Balakumar Chandrasekarn, Published Year: 2021

Faculty: Pharmacy

Abstract: The uncontrolled growth of abnormal cells is generally determined by the alterations in genes and epigenetic factors. Oncological research is undergoing a drastic revolution due to advanced technology improvement in the verge of exploring the relationship of molecules which make a unit cell of an organism. Molecular biologists are more aware about the genomic, transcriptomic, and proteomic data because of the obvious technology advancement in the area of molecular medicine. This has further lead to the development of novel potential targets for drug development and also establishment of molecular markers for unified treatment and therapy against cancer. Numerous cancer studies have been carried out using altered protocols, samples, and data from multiple sources in order to compare and validate new strategies with the conventional ones. Moreover, it also opens a wide arena to develop personalized or stratified medicine to counter medicinal upheaval. Bioinformatics helps to develop new methods and advancing trends in order to attain the ultimate goal of developing therapeutics and diagnostic protocols in the area of cancer research

Keywords: Bioinformatics; cancer detection

Research Title: Nanocarriers in novel drug delivery system

Author: Balakumar Chandrasekarn, Published Year: 2021

Faculty: Pharmacy

Abstract: If the particle exhibits a dimension range of 1–100 nm, then it is designated as a nanoparticle (NP), which upon incorporation precisely into the materials with suitable engineering process enables us to show characteristic physicochemical properties. They are organized in the drug formulations in a special manner so that they can target specifically to particular tissues or cells without disturbing surrounding healthy host cells. There are mainly two methods available to construct nanoparticles, namely bottom-up technique and bottom-down technique. If the nanoparticles are constructed through atom-by-atom, then it is known as the bottom-up technique, whereas the bottom-down technique involves the fabrication of nanoparticles through the elimination of existing atoms and assembling the basic units to defined structures

Keywords: Nanocarriers; novel drug delivery system

Research Title: Pharmacology of Adenosine Receptors

Author: Balakumar Chandrasekarn, Published Year: 2020

Faculty: Pharmacy

Abstract: Adenosine is an endogenous nucleoside molecule, regulating a myriad of physiological and pathological effects in almost all the organs systems including central nervous system (CNS), cardiovascular system (CVS), respiratory system, renal system, and immune system. Biological functions of adenosine are mediated by its interactions with four subtypes of G-protein-coupled receptors (GPCRs), namely A1, A2A, A2B, and A3 adenosine receptors (ARs) which are ubiquitously present throughout the body. However, ubiquitous distribution of ARs in both healthy and diseased tissues imposed a great challenge to the researchers in the discovery and development of ligands targeting a particular AR subtype in a specific tissue, devoid of undesirable side effects

Keywords: Adenosine · A1, A2A, A2B and A3 adenosine receptors · G-protein-coupled receptors (GPCRs) · Adenosine receptors signaling

Research Title: Drug-Receptor Interactions

Author: Balakumar Chandrasekarn, Published Year: 2020

Faculty: Pharmacy

Abstract: Conventional treatment of any disease can be achieved by the administration of drugs of natural and synthetic origin. The drug exhibits its pharmacological action by altering cellular signaling or the biochemical events associated with the respective target proteins such as receptors or enzymes. Functional groups/ pharmacophores of the drug interact with functional groups present in the receptor’s binding site, complementarily thereby producing effective binding interactions. Key interactions that occur between the drug and the receptor will decide the potency and intrinsic activity of the drug. Major interactions observed in the drug-receptor complexes are mostly of reversible type which consist of electrostatic interactions, ion-dipole and dipole-dipole interactions, hydrogen bonding, charge-transfer interactions, hydrophobic, and Van der Waals interactions. In this chapter, we have discussed the types of receptors, theories and types of drug-receptor interactions, the role of functional groups, and

Keywords: Drug-receptor complex · H-bonding · VdW interaction · Antagonist · Agonist

Research Title: A system for prediction, prevention, and diagnosis of heart related diseases at an early stage using deep learning

Author: Balakumar Chandrasekarn, Published Year: 2022

Faculty: Pharmacy

Abstract: A system for prediction, prevention, and diagnosis of heart related diseases at an early stage using deep learning

Keywords: A system; prediction; prevention; deep learning