Drug repurposing using computational methods to identify therapeutic options for COVID-19

Mahdian, Soodeh; Ebrahim‐Habibi, Azadeh; Zarrabi, Mahboobeh

doi:10.1007/s40200-020-00546-9

Cited by 60 publications

(48 citation statements)

References 31 publications

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“…Some examples of potential disruptors of the S glycoprotein interaction with ACE2, identi ed by simple molecular docking of approved drugs include hesperidin [72], paritaprevir [44], cladribine, clofarabine, and udarabine [14]. Differently, docking combined with MD simulations highlighted denopamine, bometolol, naminterol, rotigaptide, benzquercin [19], simeprevir, lumacaftor [63], tegobuvir, bromocriptine, baicalin [6], KT185, KT203, GSK1838705A, and BMS195614 [9] as potential binders of the RBD.…”

Section: Introductionmentioning

confidence: 99%

Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein

Deganutti

Prischi

Reynolds

2020

Preprint

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The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The first interaction between the virus and the host cell is mediated by the spike protein on the virus surface and the human angiotensin-converting enzyme (ACE2). Small molecules able to bind the receptor-binding domain (RBD) of the spike protein and disrupt the binding to ACE2 would offer an important tool for slowing, or even preventing, the infection. Here, we screened 2421 approved small molecules in silico and validated the docking outcomes through extensive molecular dynamics simulations. Out of six drugs characterized as putative RBD binders, the cephalosporin antibiotic cefsulodin was further assessed for its effect on the binding between the RBD and ACE2, suggesting the importance of considering the dynamic formation of the heterodimer when judging any potential candidate.

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Section: Introductionmentioning

confidence: 99%

Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein

Deganutti

Prischi

Reynolds

2020

Preprint

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“…3C-like protease (3CLpro), papain-like protease (PLpro), and spike protein [6]. However, the tendency of the virus to mutate itself gets increased if the right dose-right time-right drug is not chosen.…”

Section: Introductionmentioning

confidence: 99%

Withanolides from Withania somnifera as an immune booster and their therapeutic option against COVID-19

Khanal

Patil

Pasha

et al. 2020

Preprint

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Aim: The present study aimed to investigate the withanolides as an immune system booster and anti-viral agents against the coronavirus.Materials and Methods: Reported withanolides from Withinana somnifera were retrieved from the open-source database i.e. ChEBI, PCIDB and Dr. Duke's Phytochemical and Ethnobotanical Databases. Their protein-based targets were predicted using DigepPred and the protein-protein interaction was evaluated using STRING. Similarly, the drug-likeness score of individual compounds was predicted using MolSoft and intestinal absorptivity was predicted using the boiled-egg model. The network among the compounds, proteins, and modulated pathways was constructed using Cytoscape and the docking was performed using autodock4.0.Results: Withanoloid Q was predicted to modulate the highest number of proteins, showed positive human intestinal absorption and had the highest druglikeness score. Similarly, combined network interaction identified withanolide Q to target the highest number of proteins; RAC1 was majorly modulated and regulating Fluid shear stress and atherosclerosis as a majorly regulated pathway. Similarly, Withanolide D and Withanolide G were predicted to have the better binding affinity with PLpro, Withanolide M with 3clpro, and Withanolide M with spike protein based on binding energy and number of hydrogen bond interactions. Conclusion: Among the multiple withanolides from Withania somnifera, withanolide-D, -G, -M, and -Q were predicted as a lead hit based on druglikeness score, modulated proteins, and docking score to boost immune system and inhibit the COVID infection.

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“…Hence, it is important to identify any alternative approach as prophylaxis against COVID-19 which can be implemented via the utilization of immune boosters from natural sources. Three targets 3C-like protease (3CLpro), papain-like protease (PLpro), and spike protein [3][4][5][6] are being targeted by multiple investigators to identify the new hit molecule for the management of COVID-19. Further, in COVID-19 infection severe in ammation and cell necrosis are contributing to the worsening of pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Anthraquinone derivatives as an immune booster and their therapeutic option against COVID-19

Khanal

Patil

Chand

et al. 2020

Preprint

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Multiple Anthraquinolines derivatives are reported for their immune-boosting, anti-inflammatory and anti-viral efficacy. Hence, the present study dealt to investigate the reported anthraquinone derivatives as an immune booster molecule in COVID-19 infection and evaluate their binding affinity with three reported targets of novel coronavirus i.e. 3CLpro, PLpro and spike proteins. The reported anthraquinone derivatives were retrieved from an open-source database and filtered based on a positive druglikeness score. Further, the probably modulated gene by compounds with positive druglikeness score was evaluated for the modulation of proteins using DIGEP-Pred and the interaction of proteins was evaluated using STRING; associated pathways were recorded concerning the KEGG pathway database. Finally, docking was carried using autodock4; pose scoring minimum binding energy was chosen to visualize the ligand-protein interaction. Among 101 compounds, 36 scored positive druglikeness scores; modulating multiple pathways for immune-boosting as well as pathways involved in infectious and non-infectious diseases. Similarly, docking study revealed torososide B to have the highest binding affinity with PLpro and 3clpro and 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone-3-O-(6'-O-acetyl)-β-D-xylopyranosyl-(1->2)-β-D-glucopyranoside with spike protein

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Drug repurposing using computational methods to identify therapeutic options for COVID-19

Cited by 60 publications

References 31 publications

Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein

Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein

Withanolides from Withania somnifera as an immune booster and their therapeutic option against COVID-19

Anthraquinone derivatives as an immune booster and their therapeutic option against COVID-19

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