In silico studies on therapeutic agents for COVID-19: Drug repurposing approach

Shah, Bhumi; Modi, Palmi; Sagar, Sneha R.

doi:10.1016/j.lfs.2020.117652

Cited by 341 publications

(311 citation statements)

References 25 publications

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“…Recently few drugs have been sent for clinical trials and few of them have even passed second stage. The drug and vaccine discovery process is still on and no lead has come in market as an armamentarium against the disease [16,44] till date. Therefore, there is a need of therapeutics still persist.…”

Section: Resultsmentioning

confidence: 99%

Canthin-6-One 9-O-Beta-Glucopyranoside: an inhibitor of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro

Verma¹,

Mitra²,

Kamboj³

et al. 2020

Preprint

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The rapid spread of SARS-CoV-2 has raised a severe global public health issue, where therapy is not identified with specific drugs or vaccines. The present investigation dealt with the inhibition of various proteins and receptors of virus using phytocompounds of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata. Phytocompounds known to have antiviral properties were screened against the papain-like protease (PLpro) and main protease (Mpro) / 3-chymotrypsin-like Protease (3CLpro). Molecular docking with Canthin-6-One 9-O-Beta-Glucopyranoside showed the highest binding affinity and least binding energy with both the proteases viz. PLpro and Mpro/ 3CLpro. ADMET analysis of the compound suggested that it is having drug-like properties like high gastrointestinal (gi-) absorption, no blood-brain barrier permeability, and high lipophilicity.

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Section: Resultsmentioning

confidence: 99%

Canthin-6-One 9-O-Beta-Glucopyranoside: an inhibitor of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro

Verma¹,

Mitra²,

Kamboj³

et al. 2020

Preprint

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“…To our knowledge, direct determination of the inhibition e cacy of HIV PIs against SARS-CoV-2 M pro in cell culture has not yet been attempted, although many in silico studies analyzing interaction between SARS-CoV-2 M pro and potential inhibitors were published [20][21][22][23][24][25][26] (Supplementary Table 1). Antiviral assays using lopinavir and ritonavir in Calu-3 cells were previously carried out for MERS-CoV, and the IC 50 for lopinavir, ritonavir and their combination was 11.6, 24.9, and 8.5 µM respectively [3].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2’s main protease

Mahdi

Mótyán

Szojka

et al. 2020

Preprint

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Abstract Background The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of infections worldwide. While the search for an effective antiviral is still ongoing, experimental therapies based on repurposing of available antivirals is being attempted, of which HIV protease inhibitors (PIs) have gained considerable interest. Inhibition profiling of the PIs directly against the viral protease has never been attempted in vitro, and while few studies reported an efficacy of lopinavir and ritonavir in SARS-CoV-2 context, the mechanism of action of the drugs remains to be validated. Methods We carried out an in-depth analysis of the efficacy of HIV PIs against the main protease of SARS-CoV-2 (Mpro) in cell culture and in vitro enzymatic assays, using a methodology that enabled us to focus solely on any potential inhibitory effects of the inhibitors against the viral protease. Results Lopinavir, ritonavir, darunavir, saquinavir, and atazanavir were able to inhibit the viral protease in cell culture, albeit in concentrations much higher than their achievable plasma levels, given their current drug formulations. While inhibition by lopinavir was attributed to its cytotoxicity, ritonavir was the most effective of the panel, with IC50 of 13.7 µM. Atazanavir on the other hand was the only PI to inhibit the viral protease both in cell culture and in our in vitro enzymatic assay. Conclusion Targeting of SARS-CoV-2 Mpro by some of the HIV PIs might be of limited clinical potential, given the high concentration of the drugs required to achieve significant inhibition. Therefore, given their weak inhibition of the viral protease, any potential beneficial effect of the PIs in COVID-19 context might perhaps be attributed to acting on other molecular target(s), rather than SARS-CoV-2 Mpro.

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“…These drugs have also been reported to inhibit HIV protease, a member of β-coronavirus, due to their therapeutic bene ts as antivirals. Lopinavir was shown to have the best therapeutic bene t compared to ritonavir 24 . In addition to nel navir and lopinavir, the results of this study show that vitamin D in potent as an inhibitor of Mpro.…”

Section: Discussionmentioning

confidence: 99%

Molecular Docking Studies of SARS-Cov-2 Mainprotease Potential Inhibitors

Utami¹,

Fitriani

Aziz

et al. 2020

Preprint

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BACKGROUND : SARS-Cov-2 causes an coronavirus disease 2019 (COVID-19), and the vaccines or drugs of this disease have not been found to inhibit this replication of the virus. Researchers are engaged in all fields of study to discover new potential inhibitors. This study aimed to compute the binding energy (BE) and interactions between the new potential inhibitors and the SARS-Cov-2 Mainprotease (Mpro).METHODS: In this study, we docked between twenty-seven patented drugs and the Mpro receptor (PDB ID: 6W63). The molecular docking calculation was performed using AutoDock Tools 1.5.6. software. Moreover, the information about the biological activity of ligands was calculated using the PASS online server. The result of the calculation was then analyzed and visualized using Biovia Discovery Studio Visualizer. Further calculation, such as the ligand-protein interaction using STITCH database and Lipinski’s rule five were employed in this research.RESULTS: The molecular docking calculation results showed that nelfinavir was strongly bound to Mpro with BE of -9,51 kcal/mol, followed by lopinavir, vitamin D, ritonavir, and dexamethasone. From these ligands, we considered dexamethasone because this ligand works as an anti-inflammatory agent. CONCLUSIONS: Following the calculation, nelfinavir, lopinavir, and dexamethasone are proposed as a potential inhibitor of the Mpro receptor, but there is a need for further investigation.

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In silico studies on therapeutic agents for COVID-19: Drug repurposing approach

Cited by 341 publications

References 25 publications

Canthin-6-One 9-O-Beta-Glucopyranoside: an inhibitor of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro

Canthin-6-One 9-O-Beta-Glucopyranoside: an inhibitor of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro

Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2’s main protease

Molecular Docking Studies of SARS-Cov-2 Mainprotease Potential Inhibitors

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