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

Panda, Subhamay; Kumari, Leena; Badwaik, Hemant Ramachandra; Shanmugarajan, Dhivya

doi:10.1016/b978-0-323-91172-6.00008-x

Cited by 4 publications

(4 citation statements)

References 60 publications

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“…Asp22, Ile23, Val49, Ala154, Gly130, Phe132, Asn40, Gly46, Lys44, Gly48, Ala50, Ser128, and Ile131 were found to interact with the native ligand. This information was used for the generation of an imaginary grid-box for further studies [ 49 , 50 ]. Table 1 shows the grid coordinates used to create the grid box, and the docking outcome of ADP ribose against ARP enzyme is tabulated in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

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Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2

Kciuk

Mujwar

Rani³

et al. 2022

Molecules

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Coronavirus Disease-2019 (COVID-19) is a highly contagious disease caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) classified the disease a as global public health hazard on 11 March 2020. Currently, there are no adequate measures to combat viral infections, including COVID-19, and the medication guidelines for the management of COVID-19 are dependent on previous findings from SARS-CoV and MERS-CoV research. Natural products have achieved widespread acceptance around the world as a means of enhancing healthcare and disease prevention. Plants are a potential source of antiviral factors such as flavonoids, phenolic acids, terpenoids, and others. Some of these agents exhibit a broad spectrum of antiviral activity. This study aimed to screen herbal leads for possible inhibitors of the SARS-CoV-2 ADP Ribose Phosphatase enzyme (ARP). Guggulsterone was found to be highly stabilized within the active site of the viral ARP enzyme by molecular dynamic simulation with very little fluctuation throughout the simulation timeframe of 100 ns. Thus, guggulsterone can be further used to develop a safe and competent medication for evolving therapy against SARS-CoV-2 in post-preclinical and clinical trials.

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Section: Resultsmentioning

confidence: 99%

“…Drug repurposing and repositioning approaches are now frequently used to develop successful novel medicines for various conditions using drugs already used in the clinic. Computational methodologies such as structure-based drug design can be used to improve the efficiency and accuracy of drug discovery [ 8 , 39 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2

Kciuk

Mujwar

Rani³

et al. 2022

Molecules

View full text Add to dashboard Cite

show abstract

“…Given that the development of new medications is a time-consuming process, the repurposing of existing medications for other indications may prove to be a viable alternative. However, most studies that have implemented computational methods to identify drug repurposing candidates for COVID-19 have so far leveraged diseasegene associations, protein-protein interaction, and drug-target data but less consideration is given to the interactions between other biomedical and molecular features specific to different COVID-19 disease phases, such as recorded in large scale multi-omics profiling efforts [26][27][28][29]. Applying computational multi-omics datadriven within drug data approaches to the repurposing of existing medications is, in fact, a potentially and highly efficient means of drug discovery since the pharmacological properties, formulations, and toxicities of such agents are already known [26][27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

“…However, most studies that have implemented computational methods to identify drug repurposing candidates for COVID-19 have so far leveraged diseasegene associations, protein-protein interaction, and drug-target data but less consideration is given to the interactions between other biomedical and molecular features specific to different COVID-19 disease phases, such as recorded in large scale multi-omics profiling efforts [26][27][28][29]. Applying computational multi-omics datadriven within drug data approaches to the repurposing of existing medications is, in fact, a potentially and highly efficient means of drug discovery since the pharmacological properties, formulations, and toxicities of such agents are already known [26][27][28][29][30][31][32]. In this study, we explore the utility of incorporating disease-state specific omics-graph along with drug-related data to identify drug repurposing candidates for mild, moderate, or severe COVID-19 disease states.…”

Section: Introductionmentioning

confidence: 99%

Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases

Agamah,

Ederveen,

Skelton

et al. 2024

Preprint

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Background:The development and roll-out of vaccines, and the use of various drugs have contributed to controlling the COVID-19 pandemic. Nevertheless, challenges such as the inequitable distribution of vaccines, the influence of emerging viral lineages and immune evasive variants on vaccine efficacy, and the inadequate immune defense in subgroups of the population continue to motivate the development of new drugs to combat the disease. Aim:In this study, we sought to identify, prioritize, and characterize drug repurposing candidates appropriate for treating mild, moderate, or severe COVID-19 using a network-based integrative approach that systematically integrates drug-related data and multi-omics datasets. Methods: We leveraged drug data, and multi-omics data, and used a random walk restart algorithm to explore an integrated knowledge graph comprised of three sub-graphs: (i) a COVID-19 knowledge graph, (ii) a drug repurposing knowledge graph, and (iii) a COVID-19 disease-state specific omics graph. Results:We prioritized twenty FDA-approved agents as potential candidate drugs for mild, moderate, and severe COVID-19 disease phases. Specifically, drugs that could stimulate immune cell recruitment and activation including histamine, curcumin, and paclitaxel have potential utility in mild disease states to mitigate disease progression. Drugs like omacetaxine, crizotinib, and vorinostat that exhibit antiviral properties and have the potential to inhibit viral replication can be considered for mild to moderate COVID-19 disease states. Also, given the association between antioxidant deficiency and high inflammatory factors that trigger cytokine storms, antioxidants like glutathione can be considered for moderate disease states. Drugs that exhibit potent anti-inflammatory effects like (i) anti-inflammatory drugs (sarilumab and tocilizumab), (ii) corticosteroids (dexamethasone and hydrocortisone), and (iii) immunosuppressives (sirolimus and cyclosporine) are potential candidates for moderate to severe disease states that trigger a hyperinflammatory cascade of COVID-19. Conclusion:Our study demonstrates that the multi-omics data-driven integrative analysis within the drug data enables prioritizing drug candidates for COVID-19 disease phases, offering a comprehensive basis for therapeutic strategies that can be brought to market quickly given their established safety profiles. Importantly, the multi-omics data-driven integrative analysis within the drug data approach implemented here can be used to prioritize drug repurposing candidates appropriate for other diseases.

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Drug Repositioning: A Monetary Stratagem to Discover a New Application of Drugs

Rohilla,

Rohilla

2024

CDDT

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Drug repurposing, also referred to as drug repositioning or drug reprofiling, is a scientific approach to the detection of any new application for an already approved or investigational drug. It is a useful policy for the invention and development of new pharmacological or therapeutic applications of different drugs. The strategy has been known to offer numerous advantages over developing a completely novel drug for certain problems. Drug repurposing has numerous methodologies that can be categorized as target-oriented, drug-oriented, and problem-oriented. The choice of the methodology of drug repurposing relies on the accessible information about the drug molecule and like pharmacokinetic, pharmacological, physicochemical, and toxicological profile of the drug. In addition, molecular docking studies and other computer-aided methods have been known to show application in drug repurposing. The variation in dosage for original target diseases and novel diseases presents a challenge for researchers of drug repurposing in present times. The present review critically discusses the drugs repurposed for cancer, covid-19, Alzheimer’s, and other diseases, strategies, and challenges of drug repurposing. Moreover, regulatory perspectives related to different countries like the United States (US), Europe, and India have been delineated in the present review.

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

Cited by 4 publications

References 60 publications

Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2

Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2

Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases

Drug Repositioning: A Monetary Stratagem to Discover a New Application of Drugs

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