Insights into the inhibitory potential of selective phytochemicals against Mpro of 2019-nCoV: a computer-aided study

Rasool, Nouman; Akhtar, Ammara; Hussain, Waqar

doi:10.1007/s11224-020-01536-6

Cited by 28 publications

(25 citation statements)

References 32 publications

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“…These energies can characterize the electrophilic or nucleophilic nature of a compound. Therefore, the screened phytochemicals illustrated the higher reactivity of these phytochemicals, as reported in various previous studies [ 23 – 25 , 27 , 30 – 33 , 35 , 52 , 65 ].…”

Section: Resultssupporting

confidence: 80%

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Phytochemicals from Selective Plants Have Promising Potential against SARS-CoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations

Kousar¹,

Majeed

Yasmin

et al. 2020

BioMed Research International

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Coronaviruses have been reported previously due to their association with the severe acute respiratory syndrome (SARS). After SARS, these viruses were known to be causing Middle East respiratory syndrome (MERS) and caused 35% evanescence amid victims pursuing remedial care. Nowadays, beta coronaviruses, members of Coronaviridae, family order Nidovirales, have become subjects of great importance due to their latest pandemic originating from Wuhan, China. The virus named as human-SARS-like coronavirus-2 contains four structural as well as sixteen nonstructural proteins encoded by single-stranded ribonucleic acid of positive polarity. As there is no vaccine available to treat the infection caused by these viruses, there is a dire need for taking necessary steps against this virus. Herein, we have targeted two nonstructural proteins of SARS-CoV-2, namely, methyltransferase (nsp16) and helicase (nsp13), respectively, due to their substantial activity in viral pathogenesis. A total of 2035 compounds were analyzed for their pharmacokinetics and pharmacological properties. The screened 108 compounds were docked against both targeted proteins and were compared with previously reported known compounds. Compounds with high binding affinity were analyzed for their reactivity through DFT analysis, and binding was analyzed using molecular dynamics simulations. Through the analyses performed in this study, it is concluded that EryvarinM, Silydianin, Osajin, and Raddeanine can be considered potential inhibitors for MTase, while TomentodiplaconeB, Osajin, Sesquiterpene Glycoside, Rhamnetin, and Silydianin for helicase after these compounds are validated thoroughly using in vitro and in vivo protocols.

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Section: Resultssupporting

confidence: 80%

“…Repurposing of drugs is a remarkable approach to opt antiviral compounds as COVID-19 drug candidates [ 57 ]. Recently, a study has been reported targeting the main protease of SARS-CoV-2, using a set of phytochemicals [ 30 ]. However, herein, another set of phytochemicals has been used to target MTase and helicase.…”

Section: Resultsmentioning

confidence: 99%

Phytochemicals from Selective Plants Have Promising Potential against SARS-CoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations

Kousar¹,

Majeed

Yasmin

et al. 2020

BioMed Research International

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“…The intermediate is mixed with p-toluenesulfonyl chloride and triethylamine to activate the acid function, followed by the addition of reagent (74) in a one-pot procedure. The condensation allows the formation of intermediate (75), which is submitted to acidic conditions for a Boc deprotection, followed by another nucleophilic additionelimination reaction with reagent (76), thus obtaining the final product ritonavir (2) ( Fig. 16).…”

Section: Patent Protection and Synthesis Of Repositionable Drugsmentioning

confidence: 99%

“… 68 , 70 , 73 M pro has been widely explored in drug discovery campaigns using experimental and/or computational approaches. 68 , 73 , 74 , 75 , 76 , 77 Moreover, M pro has no human homologue, which reduces the chances of toxic effects of a given inhibitor. 68 Potential SARS-CoV-2 M pro inhibitors include FDA-approved antivirals, such as inhibitors of HIV-1 [e. g., lopinavir (1) /ritonavir (2)] and HCV [e.g., boceprevir (3)] proteases, as well as antineoplastic [e.g.…”

mentioning

confidence: 99%

COVID-19: molecular targets, drug repurposing and new avenues for drug discovery

Senger

Evangelista

Dantas

et al. 2020

Mem. Inst. Oswaldo Cruz

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Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.

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“…Docking simulation was repeated. During virtual screening with AutoDock Vina 4.2 complex formation was achieved by allowing all rotatable bonds of the chemical ligands free choice of torsional degrees of freedom and Rapid Grid-Based (RGB) energy evaluation (Rasool et al, 2020).…”

Section: Active Site Predictionmentioning

confidence: 99%

Molecular Docking Analyses of Phytochemicals Obtained from African Antiviral Herbal Plants Exhibit Inhibitory Activity against Therapeutic Targets of SARS-CoV-2

Dogo¹,

Uchechukwu²,

Umar³

et al. 2020

Preprint

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Presently, the global public health threat of international concern is the coronavirus disease-2019 (COVID-19), a viral disease of worldwide prevalence caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), at present the disease has no known cure or vaccine. Plants worldwide including plants of African ethnopharmacological relevance are a natural source of abundant and diverse phytochemicals with bioactivity against microorganisms including viruses. We selected 13 plants used in African traditional medicine for the treatment of viral diseases to screen for phytochemicals capable of interfering with SARS-CoV-2 therapeutic targets using AutoDock Vina in silico tool. 25 phytochemicals from these plants that passed the Lipinski rule of drug-likeness were assessed for antiviral activity against three SARS-CoV-2 therapeutic targets, namely: spike glycoprotein, Papain-like protease and 3C-like proteinase. The crystal structure of the viral protein targets was obtained from the protein databank website (https://www.rcsb.org/). The active sites of the target proteins were predicted using SCFBio Server (http://www.scfbio-iitd.res.in/dock/ActiveSite.jsp) from the PDB file as input. The antiviral herbal phytochemical compounds were then docked with prepared targets: Papain-like protease, 3C-like proteinase and spike glycoprotein. The Autodocking hit results generated six lead phytochemicals out of a library of twenty-five (25) phytochemicals from the African traditional herbs with potential anti-SARS-CoV-2 activity. The lead molecules with their binding affinities against Papain-like protease and 3C-Like Proteinase are as follows: Ginsenosides (-9.9 kcal/mol), ursolic acid (-9.4 kcal/mol), oleanolic acid (-9.4 kcal/mol), cynarine (-8.9 kcal/mol), glabridin (-8.5 kcal/mol) and cinnamoyl-echinadiol (-8.2 kcal/mol). ADMET profile shows glabridin, cinnamoyl-echinadiol and neral obtained from Licorice, Echinacea purpurea and lemongrass respectively, exhibited best-fit values as drugs candidate. We advocate for further in vitro and in vivo studies to evaluate the activity of these lead compounds with a view to optimized drug intervention against COVID-19 pandemic.

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Insights into the inhibitory potential of selective phytochemicals against Mpro of 2019-nCoV: a computer-aided study

Cited by 28 publications

References 32 publications

Phytochemicals from Selective Plants Have Promising Potential against SARS-CoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations

Phytochemicals from Selective Plants Have Promising Potential against SARS-CoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations

COVID-19: molecular targets, drug repurposing and new avenues for drug discovery

Molecular Docking Analyses of Phytochemicals Obtained from African Antiviral Herbal Plants Exhibit Inhibitory Activity against Therapeutic Targets of SARS-CoV-2

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