Computational Screening of DrugBank DataBase for Novel Cell Cycle Inhibitors

2016 ◽  
pp. 61-70
Author(s):  
Satyanarayana Kotha ◽  
Yesu Babu Adimulam ◽  
R. Kiran Kumar
Keyword(s):  
Cell Cycle ◽  
Computational Screening ◽  
Cell Cycle Inhibitors ◽  
Drugbank Database

Evaluation of NovelN-(piperidine-4-yl)benzamide Derivatives as Potential Cell Cycle Inhibitors in HepG2 Cells

2014 ◽  
Vol 86 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Jin Hou ◽  
Wei Zhao ◽  
Zhi-Ning Huang ◽  
Shao-Mei Yang ◽  
Li-Juan Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hepg2 Cells ◽  
Cell Cycle Inhibitors ◽  
Benzamide Derivatives

scholarly journals Development of Cell Cycle Inhibitors for Cancer Therapy

2009 ◽  
Vol 16 (2) ◽  
Author(s):  
Gary K. Schwartz ◽  
Mark Dickson
Keyword(s):  
Cell Cycle ◽  
Cancer Therapy ◽  
Cell Cycle Inhibitors

scholarly journals Effects of Cell Cycle Inhibitors on Tau Phosphorylation in N2aTau3R Cells

2008 ◽  
Vol 35 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Concepcion Conejero-Goldberg ◽  
Kirk Townsend ◽  
Peter Davies
Keyword(s):  
Cell Cycle ◽  
Tau Phosphorylation ◽  
Cell Cycle Inhibitors

Future Therapy for HBV: Role of Cell Cycle Inhibitors

2016 ◽  
Vol 15 (4) ◽  
pp. 245-251 ◽  
Author(s):  
Mayur Brahmania ◽  
Harry L. A. Janssen
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Inhibitors ◽  
Future Therapy

scholarly journals Complex regulation of cell-cycle inhibitors by Fbxw7 in mouse embryonic fibroblasts

Oncogene ◽  
2009 ◽  
Vol 29 (12) ◽  
pp. 1798-1809 ◽  
Author(s):  
K Masuda ◽  
Y Ishikawa ◽  
I Onoyama ◽  
M Unno ◽  
I M de Alborán ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Complex Regulation ◽  
Regulation Of Cell Cycle ◽  
Cell Cycle Inhibitors

scholarly journals Searching for target-specific and multi-targeting organics for Covid-19 in the Drugbank database with a double scoring approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Natarajan Arul Murugan ◽  
Sanjiv Kumar ◽  
Jeyaraman Jeyakanthan ◽  
Vaibhav Srivastava
Keyword(s):  
Chemical Space ◽  
Specific Binding ◽  
Cost Effective ◽  
Binding Energies ◽  
Yield Potential ◽  
Computational Screening ◽  
Rigorous Research ◽  
Traditional Drug ◽  
Drugbank Database ◽  
Screening Approaches

Abstract The current outbreak of Covid-19 infection due to SARS-CoV-2, a virus from the coronavirus family, has become a major threat to human healthcare. The virus has already infected more than 44 M people and the number of deaths reported has reached more than 1.1 M which may be attributed to lack of medicine. The traditional drug discovery approach involves many years of rigorous research and development and demands for a huge investment which cannot be adopted for the ongoing pandemic infection. Rather we need a swift and cost-effective approach to inhibit and control the viral infection. With the help of computational screening approaches and by choosing appropriate chemical space, it is possible to identify lead drug-like compounds for Covid-19. In this study, we have used the Drugbank database to screen compounds against the most important viral targets namely 3C-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp) and the spike (S) protein. These targets play a major role in the replication/transcription and host cell recognition, therefore, are vital for the viral reproduction and spread of infection. As the structure based computational screening approaches are more reliable, we used the crystal structures for 3C-like main protease and spike protein. For the remaining targets, we used the structures based on homology modeling. Further, we employed two scoring methods based on binding free energies implemented in AutoDock Vina and molecular mechanics—generalized Born surface area approach. Based on these results, we propose drug cocktails active against the three viral targets namely 3CLpro, PLpro and RdRp. Interestingly, one of the identified compounds in this study i.e. Baloxavir marboxil has been under clinical trial for the treatment of Covid-19 infection. In addition, we have identified a few compounds such as Phthalocyanine, Tadalafil, Lonafarnib, Nilotinib, Dihydroergotamine, R-428 which can bind to all three targets simultaneously and can serve as multi-targeting drugs. Our study also included calculation of binding energies for various compounds currently under drug trials. Among these compounds, it is found that Remdesivir binds to targets, 3CLpro and RdRp with high binding affinity. Moreover, Baricitinib and Umifenovir were found to have superior target-specific binding while Darunavir is found to be a potential multi-targeting drug. As far as we know this is the first study where the compounds from the Drugbank database are screened against four vital targets of SARS-CoV-2 and illustrates that the computational screening using a double scoring approach can yield potential drug-like compounds against Covid-19 infection.

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