Natural xanthone compounds as promising drug candidates against COVID-19 - An integrated molecular docking and dynamics simulation study

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease2019 (COVID-19). SARS-CoV-2 is known for its high pathogenicity and transmission due to thepresence of polybasic cleavage sites. No specific drug is available for the treatment. To identifythe potential inhibitors, we have performed molecular docking against the SARS-CoV-2 mainprotease (6Y84) with fifteen important natural xanthone compounds. The docking results showedall the compounds exhibited good binding energies and interactions with the main protease. Thevalidation of representative docking complexes through molecular dynamics simulations showedthat xanthones binds with a higher binding affinity and lower free energy than the standardligand with Brasixanthone C and Brasixanthone B on 50 ns. Natural xanthone compounds havealso passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property criteriaas well as Lipinski’s rule of five. The present integrated molecular docking and dynamicssimulations study unveil the use of xanthones as potential antiviral agents against SARS-CoV-2.

Download Full-text

Computational analysis by molecular docking of thirty alkaloid compounds from medicinal plants as potent inhibitors of SARS-CoV-2 main protease

10.21203/rs.3.rs-94752/v1 ◽

2020 ◽

Author(s):

Tunga Kuhana A. ◽

Jason T. Kilembe ◽

Aristote Matondo ◽

Khamis M. Yussuf ◽

Lauraine Nininahazwe ◽

...

Keyword(s):

Molecular Docking ◽

Medicinal Plants ◽

Computational Analysis ◽

Binding Energies ◽

Effective Drug ◽

Potential Drug ◽

Lipinski’S Rule ◽

Main Protease ◽

Lipinski’S Rule Of Five ◽

Potential Inhibitors

Abstract 2020 has been highly affected by the COVID-19 outbreak. The urgent needs for a potent and effective drug for treatment of this malignance put pressure on researchers and scientists worldwide to develop potential drug or a vaccine to resist SARS-CoV-2. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results reveal four potential inhibitors (ligands 18, 21, 23 and 24) with the highest binding energies up to 12.26 kcal/mol with good profile of ADMET, as well as fully obey the Lipinski’s rule of five.

Download Full-text

Molecular Docking and Dynamics Simulation Study of Hyrtios erectus Isolated Scalarane Sesterterpenes as Potential SARS-CoV-2 Dual Target Inhibitors

Biology ◽

10.3390/biology10050389 ◽

2021 ◽

Vol 10 (5) ◽

pp. 389

Author(s):

Sameh S. Elhady ◽

Reda F. A. Abdelhameed ◽

Rania T. Malatani ◽

Abdulrahman M. Alahdal ◽

Hanin A. Bogari ◽

...

Keyword(s):

Molecular Docking ◽

Md Simulation ◽

Protein Complexes ◽

Antiviral Agents ◽

Binding Energies ◽

Dynamics Simulation ◽

Main Protease ◽

Simulation Parameters ◽

Molecular Docking And Dynamics ◽

Dual Target

Presently, the world is under the toll of pandemic coronavirus disease-2019 (COVID-19) outbreak caused by SARS-CoV-2. Lack of effective and safe therapeutics has stressed the scientific community for developing novel therapeutics capable of alleviating and stopping this pandemic. Within the presented study, molecular docking, ADME properties and all-atom molecular dynamic (MD) simulation, along with two standard antiviral agents (lopinavir and benzopurpurin-4B), were applied to investigate 15 scalaranes sesterterpenes natural compounds, purified from the Red Sea marine sponge Hyrtios erectus, as potential COVID-19 dual-target inhibitors. Following multi-step docking within COVID-19 main protease and Nsp15 endoribonuclease cavities, nine promising drug-like compounds exhibited higher docking scores as well as better interactions with the target’s crucial residues than those of reference ligands. Compounds 2, 6, 11, and 15, were predicted to simultaneously subdue the activity of the two COVID-19 targets. Dynamics behavior of the best-docked molecules, compounds 15 and 6, within COVID-19 target pockets showed substantial stability of ligand-protein complexes as presented via several MD simulation parameters. Furthermore, calculated free-binding energies from MD simulation illustrated significant ligand’s binding affinity towards respective target pockets. All provided findings supported the utility of scalarane-based sesterterpenes, particularly compounds 15 and 6, as promising lead candidates guiding the development of effective therapeutics against SARS-CoV-2.

Download Full-text

Computational analysis by molecular docking of thirty alkaloid compounds from medicinal plants as potent inhibitors of SARS-CoV-2 main protease

SDRP Journal of Computational Chemistry & Molecular Modelling ◽

10.25177/jccmm.4.4.ra.10699 ◽

2021 ◽

Vol 4 (4) ◽

pp. 487-503

Author(s):

Tunga Kuhana A ◽

◽

Jason T. Kilembe ◽

Aristote Matondo ◽

Khamis M. Yussuf ◽

...

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Medicinal Plants ◽

Computational Analysis ◽

Potential Drug ◽

Lipinski’S Rule ◽

Main Protease ◽

Lipinski’S Rule Of Five ◽

Potential Inhibitors ◽

Therapeutic Profile

Year 2020 has been highly affected by the COVID-19 outbreak. The urgent need for a potent and effective drug for the treatment of this malignancy put pressure on researchers and scientists worldwide to develop a potential drug or a vaccine to resist SARS-CoV-2 virus. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results revealed four potential inhibitors (ligands 18, 21, 23 and 24) with 12.26 kcal/mol being the highest binding energy. Additionally, in silico drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties for the four ligands showed a good predicted therapeutic profile of druggability, and fully obey the Lipinski's rule of five as well.

Download Full-text

Exploring the Potency of Nigella sativa Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations

Indonesian Journal of Chemistry ◽

10.22146/ijc.65951 ◽

2021 ◽

Vol 21 (5) ◽

pp. 1252

Author(s):

Ari Hardianto ◽

Muhammad Yusuf ◽

Ika Wiani Hidayat ◽

Safri Ishmayana ◽

Ukun Mochammad Syukur Soedjanaatmadja

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulations ◽

Global Economy ◽

Nigella Sativa ◽

Scientific Information ◽

Dynamics Simulation ◽

Lipinski’S Rule ◽

Main Protease ◽

Dynamics Simulations

Coronavirus disease (COVID-19) is a pandemic burdening the global economy. It is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Black cumin (Nigella sativa) seed may contain antivirals for the disease since it was reported to inhibit the human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Main protease (Mpro) is a vital protein for viral replication and a promising target for COVID-19 drug development. Hence, in this study, we intended to uncover the potency of N. sativa seed as the natural source of inhibitors for SARS-CoV-2 Mpro. We collected secondary metabolites in N. sativa seed through a literature search and employed Lipinski’s rule of five as the initial filter. Subsequently, virtual screening campaigns using a molecular docking method were performed, with N3 inhibitor and leupeptin as reference ligands. The top hits were analyzed further using a molecular dynamics simulation approach. Molecular dynamics simulations showed that binding affinities of nigellamine A2 and A3 to Mpro are comparable to that of leupeptin, with median values of -43.9 and -36.2 kcal mol–1, respectively. Ultimately, this study provides scientific information regarding N. sativa seeds’ potency against COVID-19 and helps direct further wet experiments.

Download Full-text

Potential Phytopharmaceutical Constituents of Solanum Trilobatum L. as Significant Inhibitors Against COVID-19: Robust-Binding Mode of Inhibition by Molecular Docking, PASS-Aid Bioactivity and ADMET Investigations

10.26434/chemrxiv.12781754.v2 ◽

2020 ◽

Author(s):

Shanmugam Anandakumar ◽

Damodharan Kannan ◽

Eugene Wilson ◽

Kasthuri Bai Narayanan ◽

Ganesan Suresh ◽

...

Keyword(s):

Molecular Docking ◽

Binding Mode ◽

Therapeutic Drug ◽

The Novel ◽

Lipinski’S Rule ◽

Drug Candidates ◽

Main Protease ◽

Solanum Trilobatum ◽

Novel Coronavirus ◽

Potential Inhibitors

The novel coronavirus is better known as COVID–19 caused by Severe Acute Respiratory Syndrome Corona–Virus 2 (SARS–CoV–2) which initially outburst at Wuhan in China on December 2019 and spread very rapidly around the globe. Scientists from the global regions endeavours to still probe for detecting potential treatment and discover effective therapeutic drug candidates for this unabated pandemic. In our article, we reported the molecular docking, bioactivity score, ADME and toxicity prediction of the phytoconstituents of Solanum trilobatum Linn. such as Solanidine, Solasodine and a–Solanine as potential inhibitors against the main protease (Mpro) of SARS–CoV–2 tropism. The molecular docking of Solanidine, Solasodine and a–Solanine has revealed that it bounded deep into the active cavity site on the Mpro. Further, the pharmacodynamics and bioactivity profile has confirmed that the molecules obeyed the Lipinski’s rule and will be used as notably treasured lead drug candidates to pursue further biochemical and cell–based assays to explore its potential against COVID–19 pandemic. Thus, envisioning thought–provoking research certainly provide new leads for the global researchers.

Download Full-text

Potential Phytopharmaceutical Constituents of Solanum Trilobatum L. as Significant Inhibitors Against COVID-19: Robust-Binding Mode of Inhibition by Molecular Docking, PASS-Aid Bioactivity and ADMET Investigations

10.26434/chemrxiv.12781754 ◽

2020 ◽

Author(s):

Shanmugam Anandakumar ◽

Damodharan Kannan ◽

Eugene Wilson ◽

Kasthuri Bai Narayanan ◽

Ganesan Suresh ◽

...

Keyword(s):

Molecular Docking ◽

Binding Mode ◽

Therapeutic Drug ◽

The Novel ◽

Lipinski’S Rule ◽

Drug Candidates ◽

Main Protease ◽

Solanum Trilobatum ◽

Novel Coronavirus ◽

Potential Inhibitors

The novel coronavirus is better known as COVID–19 caused by Severe Acute Respiratory Syndrome Corona–Virus 2 (SARS–CoV–2) which initially outburst at Wuhan in China on December 2019 and spread very rapidly around the globe. Scientists from the global regions endeavours to still probe for detecting potential treatment and discover effective therapeutic drug candidates for this unabated pandemic. In our article, we reported the molecular docking, bioactivity score, ADME and toxicity prediction of the phytoconstituents of Solanum trilobatum Linn. such as Solanidine, Solasodine and a–Solanine as potential inhibitors against the main protease (Mpro) of SARS–CoV–2 tropism. The molecular docking of Solanidine, Solasodine and a–Solanine has revealed that it bounded deep into the active cavity site on the Mpro. Further, the pharmacodynamics and bioactivity profile has confirmed that the molecules obeyed the Lipinski’s rule and will be used as notably treasured lead drug candidates to pursue further biochemical and cell–based assays to explore its potential against COVID–19 pandemic. Thus, envisioning thought–provoking research certainly provide new leads for the global researchers.

Download Full-text

Potential Phytopharmaceutical Constituents of Solanum Trilobatum L. as Significant Inhibitors Against COVID-19: Robust-Binding Mode of Inhibition by Molecular Docking, PASS-Aid Bioactivity and ADMET Investigations

10.26434/chemrxiv.12781754.v1 ◽

2020 ◽

Author(s):

Shanmugam Anandakumar ◽

Damodharan Kannan ◽

Eugene Wilson ◽

Kasthuri Bai Narayanan ◽

Ganesan Suresh ◽

...

Keyword(s):

Molecular Docking ◽

Binding Mode ◽

Therapeutic Drug ◽

The Novel ◽

Lipinski’S Rule ◽

Drug Candidates ◽

Main Protease ◽

Solanum Trilobatum ◽

Novel Coronavirus ◽

Potential Inhibitors

The novel coronavirus is better known as COVID–19 caused by Severe Acute Respiratory Syndrome Corona–Virus 2 (SARS–CoV–2) which initially outburst at Wuhan in China on December 2019 and spread very rapidly around the globe. Scientists from the global regions endeavours to still probe for detecting potential treatment and discover effective therapeutic drug candidates for this unabated pandemic. In our article, we reported the molecular docking, bioactivity score, ADME and toxicity prediction of the phytoconstituents of Solanum trilobatum Linn. such as Solanidine, Solasodine and a–Solanine as potential inhibitors against the main protease (Mpro) of SARS–CoV–2 tropism. The molecular docking of Solanidine, Solasodine and a–Solanine has revealed that it bounded deep into the active cavity site on the Mpro. Further, the pharmacodynamics and bioactivity profile has confirmed that the molecules obeyed the Lipinski’s rule and will be used as notably treasured lead drug candidates to pursue further biochemical and cell–based assays to explore its potential against COVID–19 pandemic. Thus, envisioning thought–provoking research certainly provide new leads for the global researchers.

Download Full-text

Computational Discovery of SARS-CoV-2 NSP 16 Drug Candidates Based on Pharmacophore Modeling and Molecular Dynamics Simulation

Journal of Computational Biophysics and Chemistry ◽

10.1142/s2737416521500198 ◽

2021 ◽

Vol 20 (04) ◽

pp. 377-390

Author(s):

Zahra Hesari ◽

Samaneh Zolghadri ◽

Sajad Moradi ◽

Mohsen Shahlaei ◽

Elham Tazikeh-Lemeski

Keyword(s):

Molecular Dynamics ◽

Study Drug ◽

Pharmacophore Modeling ◽

Binding Energies ◽

Dynamics Simulation ◽

Structural Protein ◽

Drug Candidates ◽

Computational Discovery ◽

Approved Drugs ◽

Dynamics Simulations

Non-Structural Protein 16 (NSP-16) is one of the most suitable targets for discovery of drugs for corona viruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been accomplished by pharmacophore-based virtual screening among some analogs (FDA approved drugs) and marine natural plants (MNP). The comparison of the binding energies and the inhibition constants was determined using molecular docking method. Three compounds including two FDA approved (Ibrutinib, Idelalisib) and one MNP (Kumusine) were selected for further investigation using the molecular dynamics simulations. The results indicated that Ibrutinib and Idelalisib are oral medications while Kumusine, with proper hydrophilic and solubility properties, is an appropriate candidate for nsp-16 inhibitor and can be effective to control COVID-19 disease.

Download Full-text

MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i9.38485 ◽

2020 ◽

pp. 174-178

Author(s):

SHAILENDRA SANJAY SURYAWANSHI ◽

POOJA BHAVAKANA JAYANNACHE ◽

RAJKUMAR SANJAY PATIL ◽

PALLED MS ◽

ALEGAON SG

Keyword(s):

Molecular Docking ◽

Treatment Options ◽

Docking Studies ◽

Binding Energies ◽

Molecular Docking Studies ◽

Discovery Studio ◽

Main Protease ◽

Potential Inhibitors ◽

Binding Energy Calculations ◽

Native Ligand

Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease.

Download Full-text