Computational approaches for drug repositioning and repurposing to combat SARS-CoV-2 infection

Drug repositioning (also referred to as drug repurposing) is the method of exploring novel therapeutic indications for Food and Drug Administration-approved clinically implemented drugs. The unique strategy of drug repositioning is used to boost the drug development process since drug discovery is an expensive, arduous, cumbersome, and high-risk procedure. Recently, several pharmaceutical firms have used the drug repositioning technique in their drug discovery and development programs to develop new medications based on the identification of new therapeutic targets. This technique is extremely effective, saves time, is comparatively economical, and has a low chance of failure. Developing appropriate treatment measures to inhibit the spread of Coronavirus disease-2019 (COVID-19) is currently a top priority. As a result, several studies were conducted to build novel therapeutic molecules using diverse strategies of drug repurposing to discover drug candidates against COVID-19 infection that can act as substantial inhibitors against virus particles. By implementing virtual screening of drug libraries, it is possible to identify potential drugs through drug repurposing. A molecular docking approach and calculation of binding free energy are used to estimate binding affinity and drug–receptor interactions. Drug-repurposing methodologies can be divided into three categories: target-oriented, drug-oriented, and disease-oriented, based on the gathered data about the various physicochemical, pharmacokinetic and pharmacological features of a drug candidate. Using computational methods such as homology modeling and molecular similarity, this methodology aids in determining the binding interaction of drug molecules with the target protein of the virus. In this book chapter, we explore a typical set of currently utilized computational techniques for identifying repurposable drug molecules for COVID-19, as well as their supporting databases. We also assess promising drugs anticipated by computational approaches to drugs currently being evaluated in clinical trials. Moreover, we also examine the takeaways from the evaluated research efforts, such as how to competently combine bioinformatics tools with experimental work and suggest a fully integrated drug-repurposing approach to combat the deadly COVID-19 infection. © 2022 Elsevier Inc. All rights reserved.

System and network biology-based computational approaches for drug repositioning

Recent advances in computational biology have not only fastened the drug discovery process but have also proven to be a powerful tool for the search of existing molecules of therapeutic value for drug repurposing. The system biology-based drug repurposing approaches shorten the time and reduced the cost of the whole process when compared to de novo drug discovery. In the present pandemic situation, these computational approaches have emerged as a boon to tackle the COVID-19 associated morbidities and mortalities. In this chapter, we present the overview of system biology-based network system approaches which can be exploited for the drug repurposing of disease. Besides, we have included information on relevant repurposed drugs which are currently used for the treatment of COVID-19. © 2022 Elsevier Inc. All rights reserved.