Performing an In Silico Repurposing of Existing Drugs by Combining Virtual Screening and Molecular Dynamics Simulation

Sohraby, Farzin; Bagheri, Milad; Aryapour, Hassan

doi:10.1007/978-1-4939-8955-3_2

Cited by 33 publications

(21 citation statements)

References 64 publications

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“…Although drug repurposing has some limitations, but it can avoid expensive costs associated with earlystage testing of the hit compounds and facilitate the discovery of new classes of medicines (Ma et al, 2013). Recently, a review article, published by Sohraby et al, have reported the basic principles and recent advances in drug repositioning by structure-based virtual screening and highlighted the powerful synergy of in-silico techniques (Sohraby et al, 2019). So far, several studies have been done on drug discovery of SARS-CoV-2 by using drug repurposing approach (Elmezayen et al, 2020;Liu et al, 2020;Sang et al, 2020;Shah et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study

Tazikeh-Lemeski

Moradi

Raoufi

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Non-Structural Protein 16 (nsp-16), a viral RNA methyltransferase (MTase), is one of the highly viable targets for drug discovery of coronaviruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been performed by a virtual drug repurposing approach. First, drug shapebased screening (among FDA approved drugs) with a known template of MTase inhibitor, sinefungin was done and best compounds with high similarity scores were selected. In addition to the selected compounds, 4 nucleoside analogs of anti-viral (Raltgravir, Maraviroc and Favipiravir) and anti-inflammatory (Prednisolone) drugs were selected for further investigations. Then, binding energies and interaction modes were found by molecular docking approaches and compouds with lower energy were selected for further investigation. After that, Molecular dynamics (MD) simulation was carried to test the potential selected compounds in a realistic environment. The results showed that Raltegravir and Maraviroc among other compounds can bind strongly to the active site of the protein compared to sinefungin, and can be potential candidates to inhibit NSP-16. Also, the MD simulation results suggested that the Maraviroc and Raltegravir are more effective drug candidates than Sinefungin for inhibiting the enzyme. It is concluded that Raltegravir and Maraviroc which may be used in the treatment of COVID-19 after Invitro and invivo studies and clinical trial for final confirmation of drug effectiveness.

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Section: Introductionmentioning

confidence: 99%

Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study

Tazikeh-Lemeski

Moradi

Raoufi

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…Approaches in silico can be used to select drugs of interest for repurposing by using computational algorithms to recognize interactions between drugs and targets of interest. 123 The databases used vary in the drug-target interactions they explore, ranging from genomics, 124 proteomics, 125 and disease-specific and even molecular targets, among others. The idea is to identify drugs that target a certain disease mechanism, protein, or pathway that is relevant to the malignancy in question.…”

Section: Approaches To Drug Repurposingmentioning

confidence: 99%

Repurposing of Anticancer Stem Cell Drugs in Brain Tumors

Bahmad

Daher

Aljamal

et al. 2021

J Histochem Cytochem.

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Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration–approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

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“…Given the potential of the drug repurposing approach, with the combination of publicly available databases and computational methods, the in silico-based approach may provide benefits, in terms of time and cost, towards the drug discovery process by narrowing down the top hits through in silico validations [130]. Public repositories for relevant experimental and biological data, including chemical structures, gene expression, drug disease association, phenotypic traits, side effects and more, are treasure troves for in silico drug repurposing.…”

Section: In Silico Drug Repurposingmentioning

confidence: 99%

Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Gandhi

Lee

et al. 2021

IJMS

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Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.

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Performing an In Silico Repurposing of Existing Drugs by Combining Virtual Screening and Molecular Dynamics Simulation

Cited by 33 publications

References 64 publications

Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study

Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study

Repurposing of Anticancer Stem Cell Drugs in Brain Tumors

Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

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