Computational approaches for drug discovery against COVID-19

Coronavirus disease 2019 (COVID-19) has caused widespread diseases and deaths, along with the most severe social and economic disruption worldwide. Therefore, to discover potential drug candidates against COVID-19, many researchers have found various types of molecular targets and vaccine development and also explored new bioactive compounds. Although multiple vaccines have been investigated and tested, the frequent mutation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a matter of concern. In response to this devastating pandemic, a massive experimental and computational research effort has emerged to understand the disease and rapidly develop diagnostics, vaccines, and drugs. In this regard, more than 130,000 COVID-19-related research articles have been published in peer-reviewed journals. Much of the research has focused on the in silico identification of novel therapeutic candidates and the repurposing of existing drugs against COVID-19. In terms of time, the computational approaches offer the best chance to speed up the long and costly process of drug and vaccine development for a life-threatening condition such as COVID-19. Hence, researchers have given many novel drug candidates against COVID-19 by using computational techniques. In this chapter, we have described the essential computational methods and their applications that were used for COVID-19 drug discovery. This chapter provides an investigation of fundamentals, the process of the target identification, drug design, optimization, and production of the medicine for COVID-19 based on the in silico aspects of signature matching, genomics analysis, proteomics, pathogenesis, phylogenetic analysis, viral receptor binding analysis, protein-protein interaction, artificial intelligence and machine learning, drug repurposing, and deep learning (DL) methods. © 2023 Elsevier Inc. All rights reserved.

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.

A review on computational approaches that support the researches on traditional Chinese medicines (TCM) against COVID-19.

BACKGROUND: COVID-19 highly caused contagious infections and massive deaths worldwide as well as unprecedentedly disrupting global economies and societies, and the urgent development of new antiviral medications are required. Medicinal herbs are promising resources for the discovery of prophylactic candidate against COVID-19. Considerable amounts of experimental efforts have been made on vaccines and direct-acting antiviral agents (DAAs), but neither of them was fast and fully developed. PURPOSE: This study examined the computational approaches that have played a significant role in drug discovery and development against COVID-19, and these computational methods and tools will be helpful for the discovery of lead compounds from phytochemicals and understanding the molecular mechanism of action of TCM in the prevention and control of the other diseases. METHODS: A search conducting in scientific databases (PubMed, Science Direct, ResearchGate, Google Scholar, and Web of Science) found a total of 2172 articles, which were retrieved via web interface of the following websites. After applying some inclusion and exclusion criteria and full-text screening, only 292 articles were collected as eligible articles. RESULTS: In this review, we highlight three main categories of computational approaches including structure-based, knowledge-mining (artificial intelligence) and network-based approaches. The most commonly used database, molecular docking tool, and MD simulation software include TCMSP, AutoDock Vina, and GROMACS, respectively. Network-based approaches were mainly provided to help readers understanding the complex mechanisms of multiple TCM ingredients, targets, diseases, and networks. CONCLUSION: Computational approaches have been broadly applied to the research of phytochemicals and TCM against COVID-19, and played a significant role in drug discovery and development in terms of the financial and time saving.

Drug repurposing against SARS-CoV-2 using computational approaches.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated a critical need for treatments to reduce morbidity and mortality associated with this disease. However, traditional drug development takes many years, which is not practical solution given the current pandemic. Therefore, a viable option is to repurpose existing drugs. The structural data of several proteins vital for the virus became available shortly after the start of the pandemic. In this review, we discuss the importance of these targets and their available potential inhibitors predicted by the computational approaches. Among the hits identified by computational approaches, 35 candidates were suggested for further evaluation, among which ten drugs are in clinical trials (Phase III and IV) for treating Coronavirus 2019 (COVID-19).

Drug Repurposing Approaches: Existing Leads For Novel Threats And Drug Targets.

Drug Repurposing (DR) is an alternative to the traditional drug discovery process. It is cost and time effective, with high returns and low risk process that can tackle the increasing need for interventions for varied diseases and new outbreaks. Repurposing of old drugs for other diseases has gained a wider attention, as there have been several old drugs approved by FDA for new diseases. In the global emergency of COVID19 pandemic, this is one of the strategies implemented in repurposing of old anti-infective, anti-rheumatic and anti-thrombotic drugs. The goal of the current review is to elaborate the process of DR, its advantages, repurposed drugs for a plethora of disorders, and the evolution of related academic publications. Further, detailed are the computational approaches: literature mining and semantic inference, network-based drug repositioning, signature matching, retrospective clinical analysis, molecular docking and experimental phenotypic screening. We discuss the legal and economical potential barriers in DR, existent collaborative models and recommendations for overcoming these hurdles and leveraging the complete potential of DR in finding new indications.

Vaccine design of coronavirus spike (S) glycoprotein in chicken: immunoinformatics and computational approaches.

BACKGROUND: Infectious bronchitis (IB) is a highly contagious respiratory disease in chickens and produces economic loss within the poultry industry. This disease is caused by a single stranded RNA virus belonging to Cronaviridae family. This study aimed to design a potential multi-epitopes vaccine against infectious bronchitis virus spike protein (S). Protein characterization was also performed for IBV spike protein. METHODS: The present study used various tools in Immune Epitope Database (IEDB) to predict conserved B and T cell epitopes against IBV spike (S) protein that may perform a significant role in provoking the resistance response to IBV infection. RESULTS: In B cell prediction methods, three epitopes ( 1139 KKSSYY 1144 , 1140 KSSYYT 1145 , 1141 SSYYT 1145 ) were selected as surface, linear and antigenic epitopes.Many MHCI and MHCII epitopes were predicted for IBV S protein. Among them 982YYITARDMY990 and 983 YITARDMYM 991 epitopes displayed high antigenicity, no allergenicity and no toxicity as well as great linkage with MHCI and MHCII alleles. Moreover, docking analysis of MHCI epitopes produced strong binding affinity with BF2 alleles. CONCLUSION: Five conserved epitopes were expected from spike glycoprotein of IBV as the best B and T cell epitopes due to high antigenicity, no allergenicity and no toxicity. In addition, MHC epitopes showed great linkage with MHC alleles as well as strong interaction with BF2 alleles. These epitopes should be designed and incorporated and then tested as multi-epitope vaccine against IBV.