Shanthi Veerappapillai

Bio: Shanthi Veerappapillai is an academic researcher from VIT University. The author has contributed to research in topics: Medicine & Pharmacophore. The author has an hindex of 3, co-authored 10 publications receiving 35 citations.

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.

Discovery of a Potent Candidate for RET-Specific Non-Small-Cell Lung Cancer—A Combined In Silico and In Vitro Strategy

Abstract: Rearranged during transfection (RET) is a tyrosine kinase oncogenic receptor, activated in several cancers including non-small-cell lung cancer (NSCLC). Multiple kinase inhibitors vandetanib and cabozantinib are commonly used in the treatment of RET-positive NSCLC. However, specificity, toxicity, and reduced efficacy limit the usage of multiple kinase inhibitors in targeting RET protein. Thus, in the present investigation, we aimed to figure out novel and potent candidates for the inhibition of RET protein using combined in silico and in vitro strategies. In the present study, screening of 11,808 compounds from the DrugBank repository was accomplished by different hypotheses such as pharmacophore, e-pharmacophore, and receptor cavity-based models in the initial stage. The results from the different hypotheses were then integrated to eliminate the false positive prediction. The inhibitory activities of the screened compounds were tested by the glide docking algorithm. Moreover, RF score, Tanimoto coefficient, prime-MM/GBSA, and density functional theory calculations were utilized to re-score the binding free energy of the docked complexes with high precision. This procedure resulted in three lead molecules, namely DB07194, DB03496, and DB11982, against the RET protein. The screened lead molecules together with reference compounds were then subjected to a long molecular dynamics simulation with a 200 ns time duration to validate the inhibitory activity. Further analysis of compounds using MM-PBSA and mutation studies resulted in the identification of potent compound DB07194. In essence, a cell viability assay with RET-specific lung cancer cell line LC-2/ad was also carried out to confirm the in vitro biological activity of the resultant compound, DB07194. Indeed, the results from our study conclude that DB07194 can be effectively translated for this new therapeutic purpose, in contrast to the properties for which it was originally designed and synthesized.

Quinolones and Fluoroquinolones to Treat Salmonella Typhimurium: A Review of Metabolism and Pharmacokinetics

Abstract: Background Salmonella enterica serovar typhimurium is the most important serotype of Salmonella transmitted from animals to humans in most parts of the world. They are associated with an estimated 1 million deaths annually. Quinolones, an important class of broad-spectrum antimicrobials, have been utilized as a treatment option for salmonellosis for over 40 years. Despite the number of available quinolone agents, many of them failed in the clinical stage and never make it to FDA approval. Despite considerable evidence reveals the importance of different drug discovery process of S. typhimurium, there are no systematic review outlining the pharmacokinetic and pharmacodynamic parameters of quinolones. Keeping this in mind, the present study aims to provide a systematic review on metabolism and pharmacokinetics of different quinolones. Methods Information from all relevant bibliographic databases was used. Additionally, the recent journal articles and textbooks were searched manually in the preparation of this review article. Results A total of 136 journal articles and textbooks were included in the preparation of the review. Majority of research articles defines about the metabolism, pharmacodymanics and pharmacokinetics of different quinolones. Twenty eight papers outlined about the mechanism and challenges faced by the quinolones and fluoroquinolones. Finally, information on drug interactions, adverse effects and drug resistance of quinolones and fluoroquinolones were supported with forty two research articles. Note that the importance of computational biology in the field of drug discovery was also addressed with appropriate literatures. Conclusion Overall, the findings of this review highlight the importance of pharmacokinetic profiling of different quinolones in developing novel drugs to overcome drug resistance in the near future.

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

Network Pharmacology Approach for Medicinal Plants: Review and Assessment

Abstract: Natural products have played a critical role in medicine due to their ability to bind and modulate cellular targets involved in disease. Medicinal plants hold a variety of bioactive scaffolds for the treatment of multiple disorders. The less adverse effects, affordability, and easy accessibility highlight their potential in traditional remedies. Identifying pharmacological targets from active ingredients of medicinal plants has become a hot topic for biomedical research to generate innovative therapies. By developing an unprecedented opportunity for the systematic investigation of traditional medicines, network pharmacology is evolving as a systematic paradigm and becoming a frontier research field of drug discovery and development. The advancement of network pharmacology has opened up new avenues for understanding the complex bioactive components found in various medicinal plants. This study is attributed to a comprehensive summary of network pharmacology based on current research, highlighting various active ingredients, related techniques/tools/databases, and drug discovery and development applications. Moreover, this study would serve as a protocol for discovering novel compounds to explore the full range of biological potential of traditionally used plants. We have attempted to cover this vast topic in the review form. We hope it will serve as a significant pioneer for researchers working with medicinal plants by employing network pharmacology approaches.

An up-to-date overview of computational polypharmacology in modern drug discovery.

Abstract: In recent years, computational polypharmacology has gained significant attention to study the promiscuous nature of drugs. Despite tremendous challenges, community-wide efforts have led to a variet...

Proteomics approach to understand bacterial antibiotic resistance strategies.

Abstract: Introduction: The understanding of novel antibiotic resistance mechanisms is essential to develop strategies against antibiotic-resistant pathogens, which has become an urgent task due to the worldwide emergence of antibiotic resistance. Areas covered: In this review, the authors summarize the recent progress on antibiotic resistance caused by lab-evolved bacteria and clinical multidrug-resistant bacterial pathogens from the proteomics perspective. Expert opinion: Proteomics provides a new platform for a comprehensive understanding of change in protein pathways that are engaged in antibiotics resistance, which is different from a genetic view that focuses on the role of an individual gene or protein. Further work is required to understand why and how the involved pathways are integrated for surviving antibiotic-mediated killing, to use other OMICs for better comprehension of antibiotic resistance mechanisms, and to develop reprogramming proteomics, which reverts an 'antibiotic resistance proteome' to an 'antibiotic sensitive or antibiotic sensitive-like' proteome, for the control of antibiotic-resistant pathogens.