Computational methods directed towards drug repurposing for COVID-19: advantages and limitations

Sharma, Prem Prakash; Bansal, Meenakshi; Sethi, Aaftaab; Poonam, .; Pena, Lindomar; Goel, Vijay K.; Grishina, Maria; Chaturvedi, Shubhra; Kumar, Dhruv; Rathi, Brijesh

doi:10.1039/d1ra05320e

Cited by 23 publications

(14 citation statements)

References 73 publications

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“…This in silico investigation was performed using validated methods and based on past experience and expertise learned through multiple rigorous studies with other drug–target systems [ 58 , 59 , 60 ]. We are well informed of the merits of the method, but also the limits of application [ 61 , 62 ]. Computer-aided drug discovery (CADD) is a useful approach, but experimental validation (wet-lab experiments) of the in silico data will be essential [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Interaction of Camptothecin Anticancer Drugs with Ribosomal Proteins L15 and L11: A Molecular Docking Study

Bailly

Vergoten

2023

Molecules

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The antitumor drug topotecan (TPT) is a potent inhibitor of topoisomerase I, triggering DNA breaks lethal for proliferating cancer cells. The mechanism is common to camptothecins SN38 (the active metabolite of irinotecan) and belotecan (BLT). Recently, TPT was shown to bind the ribosomal protein L15, inducing an antitumor immune activation independent of topoisomerase I. We have modeled the interaction of four camptothecins with RPL15 derived from the 80S human ribosome. Two potential drug-binding sites were identified at Ile135 and Phe129. SN38 can form robust RPL15 complexes at both sites, whereas BLT essentially gave stable complexes with site Ile135. The empirical energy of interaction (ΔE) for SN38 binding to RPL15 is similar to that determined for TPT binding to the topoisomerase I-DNA complex. Molecular models with the ribosomal protein L11 sensitive to topoisomerase inhibitors show that SN38 can form a robust complex at a single site (Cys25), much more stable than those with TPT and BLT. The main camptothecin structural elements implicated in the ribosomal protein interaction are the lactone moiety, the aromatic system and the 10-hydroxyl group. The study provides guidance to the design of modulators of ribosomal proteins L11 and L15, both considered anticancer targets.

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Section: Discussionmentioning

confidence: 99%

Interaction of Camptothecin Anticancer Drugs with Ribosomal Proteins L15 and L11: A Molecular Docking Study

Bailly

Vergoten

2023

Molecules

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“…Recently, several reviews have focused on drug repurposing strategies applied to the evaluation of existing drugs for treatment of COVID-19 [32,33,[111][112][113][114][115][116][117]. Most of these reviews give an overview of potential molecular drug targets of SARS-CoV-2, the currently available therapeutic approaches for the disease, and drug repurposing as a strategy to identify new drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Computer-aided approaches applied to drug discovery against COVID-19 have mostly employed docking screen, molecular simulation, pharmacophore models, or machine learning-based virtual screens [110]. There are several reviews that summarize the use of machine learning and AI approaches in COVID-19 drug discovery [32,33,[111][112][113][114][115][116][117]. Machine learning-aided molecular docking has been frequently used for virtual screening, involving the following steps: dataset of druglike or approved molecules; crystal structure or homology model of the target; molecular docking programs; compute resources [112,118,119].…”

Section: In Silico Repurposing Strategies To Identify Potential Drugs...mentioning

confidence: 99%

Drug Repurposing for COVID-19: A Review and a Novel Strategy to Identify New Targets and Potential Drug Candidates

et al. 2022

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In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) was first identified in the province of Wuhan, China. Since then, there have been over 400 million confirmed cases and 5.8 million deaths by COVID-19 reported worldwide. The urgent need for therapies against SARS-CoV-2 led researchers to use drug repurposing approaches. This strategy allows the reduction in risks, time, and costs associated with drug development. In many cases, a repurposed drug can enter directly to preclinical testing and clinical trials, thus accelerating the whole drug discovery process. In this work, we will give a general overview of the main developments in COVID-19 treatment, focusing on the contribution of the drug repurposing paradigm to find effective drugs against this disease. Finally, we will present our findings using a new drug repurposing strategy that identified 11 compounds that may be potentially effective against COVID-19. To our knowledge, seven of these drugs have never been tested against SARS-CoV-2 and are potential candidates for in vitro and in vivo studies to evaluate their effectiveness in COVID-19 treatment.

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“…Due to this emergency, repurposing existing drugs has been an important therapeutic approach to fight the coronavirus. Computational methods are a great opportunity for preliminary filtering of drug candidates, while also saving time, effort and financial resources [48,56]. This research has aimed at developing a computational system which recommends existing drugs as potential therapeutic targets for SARS-CoV-2 making use of integrative analysis of biological data sets and artificial intelligence techniques.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to in vitro and in vivo studies, in silico studies are cheaper and faster approaches [48,55], and can be used to analyze a huge number of compounds, drug combinations and biomedical data available. Therefore, computational methods can be useful for the filtering step, and for thoroughly evaluating medications which warrant a more extensive, experimental, and clinical evaluation [43,48,56].…”

Section: Introductionmentioning

confidence: 99%

A Hybrid AI-driven Algorithm to Uncover Potential Therapeutic Targets for COVID-19 Using Network-based Drug Repurposing

Marchi¹,

Martins²

2022

Preprint

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The COVID-19 was described as a respiratory illness, however further studies recognize it as a complex heterogeneous multisystemic disorder. Global efforts have been proposed to combat COVID-19, emerging diverse therapeutic options, in which discovering new drug therapies, development of vaccines and drug repurposing have been considered the most promising approaches to fight the virus. This study aimed to repurpose known drugs for use against the COVID-19, finding better therapeutic options. Seventeen biological databases were used in this study. The genetic algorithm (GA) was performed for a set of drug target classes and COVID-19 proteins as input, whose drug candidates are obtained according to the target similarities found in the target-target similarity predictive network, resulting in a drug-target interaction network. Thus, recommended drugs correspond to the union of the drug subsets found during each GA execution. Twenty-eight drugs were indicated to be the best therapeutic targets for the virus, in special, the Cyclosporine drug was administered as adjuvant to steroid treatment for COVID-19 patients which showed positive outcomes, reducing mortality in moderate and severe cases. The drugs found have used to treat other diseases, evidencing that the COVID-19 is a multisystemic disorder and suggests that the viruses’ mechanism of action presents some comorbidity with other human diseases. Evidence shows that the drugs found in this research might act together to fight the virus in a broader fashion, however further studies including in vitro and in vivo experiments are needed to find the best combination of these drugs.

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Computational methods directed towards drug repurposing for COVID-19: advantages and limitations

Abstract: Different kind of methods utilized in expediting drug repurposing.

Cited by 23 publications

References 73 publications

Interaction of Camptothecin Anticancer Drugs with Ribosomal Proteins L15 and L11: A Molecular Docking Study

Interaction of Camptothecin Anticancer Drugs with Ribosomal Proteins L15 and L11: A Molecular Docking Study

Drug Repurposing for COVID-19: A Review and a Novel Strategy to Identify New Targets and Potential Drug Candidates

A Hybrid AI-driven Algorithm to Uncover Potential Therapeutic Targets for COVID-19 Using Network-based Drug Repurposing

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