Computational drug repurposing study of antiviral drugs against main protease, RNA polymerase, and spike proteins of SARS-CoV-2 using molecular docking method

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Alireza Jalalvand ◽  
Somayeh Behjat Khatouni ◽  
Zahra Bahri Najafi ◽  
Foroozan Fatahinia ◽  
Narges Ismailzadeh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
3D Structure ◽  
Drug Repurposing ◽  
Antiviral Drugs ◽  
Effective Drug ◽  
Main Protease ◽  
Docking Method ◽  
Inhibitory Potential ◽  
Molecular Docking Method

Abstract Objectives The new Coronavirus (SARS-CoV-2) created a pandemic in the world in late 2019 and early 2020. Unfortunately, despite the increasing prevalence of the disease, there is no effective drug for the treatment. A computational drug repurposing study would be an appropriate and rapid way to provide an effective drug in the treatment of the coronavirus disease of 2019 (COVID-19) pandemic. In this study, the inhibitory potential of more than 50 antiviral drugs on three important proteins of SARS-CoV-2, was investigated using the molecular docking method. Methods By literature review, three important proteins, including main protease, RNA-dependent RNA polymerase (RdRp), and spike, were selected as the drug targets. The three-dimensional (3D) structure of protease, spike, and RdRp proteins was obtained from the Protein Data Bank. Proteins were energy minimized. More than 50 antiviral drugs were considered as candidates for protein inhibition, and their 3D structure was obtained from Drug Bank. Molecular docking settings were defined using Autodock 4.2 software and the algorithm was executed. Results Based on the estimated binding energy of docking and hydrogen bond analysis and the position of drug binding, five drugs including, indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, had the highest inhibitory potential for all three proteins. Conclusions According to the results, among the mentioned drugs, saquinavir and lopinavir showed the highest inhibitory potential for all three proteins compared to the other drugs. This study suggests that saquinavir and lopinavir could be included in the laboratory phase studies as a two-drug treatment for SARS-CoV-2 inhibition.

scholarly journals Discovery of alliin as a putative inhibitor of the main protease of SARS-CoV-2 by molecular docking

BioTechniques ◽  
2020 ◽  
Vol 69 (2) ◽  
pp. 108-112 ◽  
Author(s):  
Bijun Cheng ◽  
Tianjiao Li
Keyword(s):  
Molecular Docking ◽  
Pharmaceutical Compounds ◽  
The Novel ◽  
Important Target ◽  
Main Protease ◽  
Docking Method ◽  
Life Threatening ◽  
Novel Coronavirus ◽  
Better Than ◽  
Molecular Docking Method

The outbreak of viral pneumonia caused by the novel coronavirus SARS-CoV-2 that began in December 2019 caused high mortality. It has been suggested that the main protease (Mpro) of SARS-CoV-2 may be an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. Remdesivir, ritonavir and chloroquine have all been reported to play a role in suppressing SARS-CoV-2. Here, we applied a molecular docking method to study the binding stability of these drugs with SARS-CoV-2 Mpro. It appeared that the ligand–protein binding stability of the alliin and SARS-CoV-2 Mpro complex was better than others. The results suggested that alliin may serve as a good candidate as an inhibitor of SARS-CoV-2 Mpro. Therefore, the present research may provide some meaningful guidance for the prevention and treatment of SARS-CoV-2.

scholarly journals Molecular Docking Unmasks Potent Phytoligands against SARS CoV 2 Spike Glycoprotein, Main Protease, Papain like Protease and RNA dependent RNA Polymerase

2020 ◽  
Vol 5 (4) ◽  
pp. 255-267
Author(s):  
Priyanka Dhar ◽  
Paushali Roy
Keyword(s):  
Molecular Docking ◽  
Oleic Acid ◽  
Rna Polymerase ◽  
Hydrophobic Interactions ◽  
Spike Glycoprotein ◽  
Rna Dependent Rna Polymerase ◽  
Ligand Interaction ◽  
Unique Challenge ◽  
Main Protease ◽  
Inhibitory Potential

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has offered a unique challenge for human survival. However, there is no available known prophylaxis, therapeutic intervention, and vaccine candidate against SARS-CoV-2 to date. We aimed towards identifying novel phytoligands from widely available botanical resources which could serve as potential inhibitors against SARS-CoV-2. Based on literature review, database search, ADMET, and drug-likeness, 55 phytoligands and 8 synthetic repurposing drugs were screened and tested against SARS-CoV-2 spike glycoprotein, main protease, papain-like protease, and RNA-dependent RNA polymerase using molecular docking and protein-ligand interaction. All phytoligands and repurposing drugs showed binding affinity based inhibitory potential against the viral proteins. The highest binding affinities of phytoligands towards antiviral targets were exhibited by colchicine and oleic acid, and that of repurposing drugs was shown by saquinavir and nelfinavir. Capsaicin, oleic acid, azithromycin, nelfinavir, remdesivir, and saquinavir were acted as plausible broad-spectrum inhibitors. Hydrogen bonds and hydrophobic interactions of amino acids were varied significantly within the conserved domain along with glutamic acid richness. Further investigation should be carried out to obtain the synergistic effect using cell-based assays, animal models, and clinical trials to discover novel phytomedicine against SARS-CoV-2.

scholarly journals Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach

2020 ◽  
Vol 13 (12) ◽  
pp. 1856-1861
Author(s):  
Purushothaman Indu ◽  
Marimuthu Ragavan Rameshkumar ◽  
Narasingam Arunagirinathan ◽  
Naif Abdullah Al-Dhabi ◽  
Mariadhas Valan Arasu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Drug Repurposing ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease

scholarly journals Investigation of potential antiviral natural products with an effect on HPV18 E6 protein by molecular docking method

2021 ◽  
Vol 11 (11) ◽  
pp. 586
Author(s):  
Mehdi Fazeli ◽  
Hosna Sarvazad ◽  
Nasrin Rahnejat ◽  
Rezvan Rostampour ◽  
Mahtab Ghanbari Rad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
3D Structure ◽  
Target Protein ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Effects ◽  
Docking Method ◽  
Hpv18 E6 ◽  
E6 Protein ◽  
Plant Compounds ◽  
Molecular Docking Method

Background: Infection with the Human Papillomavirus (HPV) causes cellular dysplasia, which leads to cervical cancers in women and penile or rectal cancers in men.        Objective: This in silico study identified the plant compounds with potential therapeutic effects against HPV 18 oncogenic virus using the molecular docking method.   Methods: The three-dimensional (3D) structure of HPV18 E6 protein, as the target protein, and the 3D structure of plant compounds with potential therapeutic effect against viruses, as ligands, was obtained from the protein databases (RCSB) and PubChem, respectively. Both structures of ligands and target protein were subjected to AutoDock tools-1.5.6, ver.4 separately. The structure with the most negative affinity was docked to reconsider its connection location. The results were analyzed more based on pharmacodynamic and pharmacokinetic parameters.     Results: The docking of HPV18 E6 protein with 19 selected ligands resulted in four compounds, curcumin, silymarin, saikosaponin c, and lactupicrin, showing the best docking scores; they had better binding free energies with HPV E6 protein. Among four compounds against HPV18 E6, silymarin and curcumin were less dangerous than other compounds due to the lack of inhibition of the human Ether-à-go-go-Related Gene (hERG). Of these two compounds, silymarin had lower oral absorption, lactopicrin had less skin absorption, lactopicrin is the substrate of P-gp, and saikosaponin c crosses the blood-brain barrier.   Conclusion: Among potential antiviral plants against HPV18E6, four compounds were found to be effective. According to these findings, it is recommended that in vitro and in vivo examinations be conducted to determine the effectiveness of these compounds against HPV18  Keywords: Biological products, Antiviral agents, HPV18, Molecular docking, Computational biology, E6 protein

scholarly journals Molecular Docking Senyawa Gingerol dan Zingiberol pada Tanaman Jahe sebagai Penanganan COVID-19

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Belinda D. P. M. Ratu ◽  
Widdhi Bodhi ◽  
Fona Budiarso ◽  
Billy J. Kepel ◽  
. Fatimawali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Amino Acid Residues ◽  
Autodock Vina ◽  
Discovery Studio ◽  
Main Protease ◽  
Docking Method ◽  
Pubmed Database ◽  
Almost All ◽  
The Impact

Abstract: COVID-19 is a new disease. Many people feel the impact of this disease. There is no definite cure for COVID-19, so many people use traditional medicine to ward off COVID-19, including ginger. This study aims to determine whether there is an interaction between compounds in ginger (gingerol and zingiberol) and the COVID-19’s main protease (6LU7). This study uses a molecular docking method using 4 main applications, namely Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, and Open Babel GUI. The samples used were gingerol and zingiberol compounds in ginger plants downloaded from Pubchem. The data used in this study used Mendeley, Clinical Key, and PubMed database. The study showed that almost all of the amino acid residues in the gingerol compound acted on the 6LU7 active site, whereas the zingiberol did not. The results of the binding affinity of ginger compounds, both gingerol and zingiberol, do not exceed the binding affinity of remdesivir, a drug that is widely researched as a COVID-19 handling drug. In conclusion, gingerol and zingiberol compounds in ginger can’t be considered as COVID-19’s treatment.Keywords: molecular docking, gingerol, zingiberol Abstrak: COVID-19 merupakan sebuah penyakit yang baru. Banyak masyarakat yang merasakan dampak dari penyakit ini. Belum ada pengobatan pasti untuk menyembuhkan COVID-19, sehingga banyak masyarakat yang menggunakan pengobatan tradisional untuk menangkal COVID-19, termasuk jahe. Penelitian ini bertujuan untuk mengetahui apakah ada interaksi antara senyawa pada jahe (gingerol dan zingiberol) dengan main protease COVID-19 (6LU7). Penelitian ini menggunakan metode molecular docking dengan menggunakan 4 aplikasi utama, yaitu Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, dan Open Babel GUI. Sampel yang digunakan yaitu senyawa gingerol dan zingiberol pada tanaman jahe yang diunduh di Pubchem. Data yang digunakan dalam penelitian ini menggunakan database Mendeley, Clinical Key, dan PubMed. Penelitian menunjukkan bahwa hampir semua residu asam amino pada senyawa gingerol bekerja pada sisi aktif 6LU7, sedangkan tidak demikian pada zingiberol. Hasil binding affinity senyawa jahe, baik gingerol maupun zingiberol tidak  melebihi binding affinity remdesivir, obat yang banyak diteliti sebagai obat penanganan COVID-19. Sebagai simpulan, senyawa gingerol dan zingiberol pada tanaman jahe tidak dapat dipertimbangkan sebagai penanganan COVID-19Kata Kunci: molecular docking, gingerol, zingiberol

scholarly journals Bhringraj Derived Phytochemicals against Pneumonia

2020 ◽  
pp. 93-96
Author(s):  
Debajani Tripathy ◽  
Chandana Adhikari ◽  
Mukundjee Pandey ◽  
Dipankar Bhattacharayay
Keyword(s):  
Molecular Docking ◽  
Life Cycle ◽  
Glutamic Acid ◽  
Interaction Energy ◽  
Plant Extract ◽  
Klebsiella Pneumonia ◽  
Discovery Studio ◽  
Docking Method ◽  
Dehydrogenase Enzyme ◽  
Molecular Docking Method

Phytochemicals from Bhringaraj plant extract are traditionally used to cure Pneumonia. It is caused by Klebsiella pneumonia. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that glutamic acid can effectively deactivate the dehydrogenase enzyme, thereby interrupting the life cycle of the organism.

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