Ramanathan Karuppasamy

Bio: Ramanathan Karuppasamy is an academic researcher from VIT University. The author has contributed to research in topics: Medicine & Pharmacophore. The author has an hindex of 4, co-authored 14 publications receiving 51 citations.

Discovery of human autophagy initiation kinase ULK1 inhibitors by multi-directional in silico screening strategies.

Abstract: Autophagy is a self-catabolic mechanism employed by cancer cells to acquire nutrients and energy in times of stress conditions, thereby leading to its progression and survival. Thus, autophagy inhibition has emerged as a new paradigm in the area of cancer treatment. Here, we leverage multi-dimensional screening campaigns aim to identify potent inhibitors against an early and an essential autophagic kinase, ULK1 from DrugBank database. In particular, receptor-based hypothesis, pharmacophore hypothesis, e-pharmacophore hypothesis and shape similarity-based screening algorithm were employed. Of note, the results of the different algorithm were then integrated to eliminate the false positive prediction. Moreover, the inhibitory activities and PK/PD parameters of the leads were tested by Glide and Qikprop algorithm. This resulted in a set of four hits namely; DB12686, DB08341, DB07936, and DB07163. Finally, molecular dynamics simulation was performed using the GROMACS package, to validate the binding kinetics of the hit compound. The compound activity in vitro was assessed by PASS algorithm, highlights the anti-cancer activities of the hits. The structural insights reveal existence of functional moieties such as piperidine carboxamide, benzenesulfonamide, benzamide, and isoindolone in the resultant hits which plays a major role in the anti-cancer activity. Overall, we strongly believe that these ULK1 antagonists could be novel and potent drug candidates for future cancer therapeutics.

Exploration of potential inhibitors for tuberculosis via structure-based drug design, molecular docking, and molecular dynamics simulation studies.

Abstract: Drug resistance in tuberculosis is major threat to human population. In the present investigation, we aimed to identify novel and potent benzimidazole molecules to overcome the resistance management. A series of 20 benzimidazole derivatives were examined for its activity as selective antitubercular agents. Initially, AutodockVina algorithm was performed to assess the efficacy of the molecules. The results are further enriched by redocking by means of Glide algorithm. The binding free energies of the compounds were then calculated by MM-generalized-born surface area method. Molecular docking studies elucidated that benzimidazole derivatives has revealed formation of hydrogen bond and strong binding affinity in the active site of Mycobacterium tuberculosis protein. Note that ARG308, GLY189, VAL312, LEU403, and LEU190 amino acid residues of Mycobacterium tuberculosis protein PrpR are involved in binding with ligands of benzimidazoles. Interestingly, the ligands exhibited same binding potential to the active site of protein complex PrpR in both the docking programs. In essence, the result portrays that benzimidazole derivatives such as 1p, 1q, and 1 t could be potent and selective antitubercular agents than the standard drug isoniazid. These compounds were then subjected to molecular dynamics simulation to validate the dynamics activity of the compounds against PrpR. Finally, the inhibitory behavior of compounds was predicted using a machine learning algorithm trained on a data collection of 15,000 compounds utilizing graph-based signatures. Overall, the study concludes that designed benzimidazoles can be employed as antitubercular agents. Indeed, the results are helpful for the experimental biologists to develop safe and non-toxic drugs against tuberculosis.

An Integrative Drug Repurposing Pipeline: Switching Viral Drugs to Breast Cancer.

Abstract: The growing incidence rate of breast cancer, coupled with cellular chemotherapeutic resistance, has made this disease one of the most prevalent cancers among women worldwide. Despite the recent efforts to understand the underlying cause of the resistance due to mutation, there are no feasible tactics to overcome this bottleneck. This issue could be addressed by the concept of polypharmacology-disguising drugs present in the pharmacopeia for novel purposes (drug repurposing). Of note, we have proposed a multi-modal computational drug-repositioning stratagem to predict drugs possessing anti-proliferative effect. Our results suggest that Ombitasvir, a Hepatitis C NS5B polymerase inhibitor, could be "repurposed" for the control and prevention of beta-tubulin-driven breast cancers. J. Cell. Biochem. 118: 1412-1422, 2017. © 2016 Wiley Periodicals, Inc.

Drug targets for COVID-19 therapeutics: Ongoing global efforts

Abstract: The current global pandemic COVID-19 caused by the SARS-CoV-2 virus has already inflicted insurmountable damage both to the human lives and global economy There is an immediate need for identification of effective drugs to contain the disastrous virus outbreak Global efforts are already underway at a war footing to identify the best drug combination to address the disease In this review, an attempt has been made to understand the SARS-CoV-2 life cycle, and based on this information potential druggable targets against SARS-CoV-2 are summarized Also, the strategies for ongoing and future drug discovery against the SARS-CoV-2 virus are outlined Given the urgency to find a definitive cure, ongoing drug repurposing efforts being carried out by various organizations are also described The unprecedented crisis requires extraordinary efforts from the scientific community to effectively address the issue and prevent further loss of human lives and health