In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis

Objective: At present, the coronavirus disease (COVID)-19 pandemic is increasing global health concerns. This coronavirus outbreak is caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. Since, no specific antiviral for treatment against COVID-19, so identification of new therapeutics is an urgent need. The objective of this study is to the analysis of lichen compounds against main protease and spike protein targets of SARS-CoV-2 using in silico approach. Methods: A total of 108 lichen compounds were subjected to ADMET analysis and 14 compounds were selected based on the ADMET properties and Lipinski’s rule of five. Molecular docking was performed for screening of selected individual lichen metabolites against the main protease and spike proteins of SARS-CoV-2 by Schrodinger Glide module software. Results: Among the lead compounds, fallacinol showed the highest binding energy value of −11.83 kcal/mol against spike protein, 4-O-Demethylbarbatic acid exhibited the highest dock score of −11.67 kcal/mol against main protease. Conclusion: This study finding suggests that lichen substances may be potential inhibitors of SARS-CoV-2.

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The dolabellane diterpenes as potential inhibitors of the SARS-CoV-2 main protease: molecular insight of the inhibitory mechanism through computational studies

RSC Advances ◽

10.1039/d1ra07584e ◽

2021 ◽

Vol 11 (62) ◽

pp. 39455-39466

Author(s):

Nanik Siti Aminah ◽

Muhammad Ikhlas Abdjan ◽

Andika Pramudya Wardana ◽

Alfinda Novi Kristanti ◽

Imam Siswanto ◽

...

Keyword(s):

In Silico ◽

Computational Studies ◽

Inhibitory Mechanism ◽

Main Protease ◽

Potential Inhibitors

An investigation on dolabellane derivatives to understand their potential in inhibiting the SARS-CoV-2 main protease (3CLpro) using an in silico approach.

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Molecular docking, pharmacophore modelling, MD simulation and in silico ADMET study reveals bitter cola constituents as potential inhibitors of SARS-CoV-2 main protease and RNA dependent-RNA polymerase

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2021.2024883 ◽

2022 ◽

pp. 1-16

Author(s):

Abimbola Peter Oluyori ◽

Bolatito Eunice Olanipekun ◽

Oluyomi Stephen Adeyemi ◽

Godshelp Osas Egharevba ◽

Abayomi Emmanuel Adegboyega ◽

...

Keyword(s):

Molecular Docking ◽

Rna Polymerase ◽

In Silico ◽

Md Simulation ◽

Rna Dependent Rna Polymerase ◽

Pharmacophore Modelling ◽

Main Protease ◽

In Silico Admet ◽

Potential Inhibitors

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Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents

Journal of Infection and Public Health ◽

10.1016/j.jiph.2021.01.016 ◽

2021 ◽

Vol 14 (5) ◽

pp. 611-619

Author(s):

Mohammad Z. Ahmed ◽

Qamar Zia ◽

Anzarul Haque ◽

Ali S. Alqahtani ◽

Omar M. Almarfadi ◽

...

Keyword(s):

In Silico ◽

Drug Repurposing ◽

Main Protease ◽

Potential Inhibitors

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Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

Molecules ◽

10.3390/molecules26061767 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1767

Author(s):

Mohamed E. Abouelela ◽

Hamdy K. Assaf ◽

Reda A. Abdelhamid ◽

Ehab S. Elkhyat ◽

Ahmed M. Sayed ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Drug Development ◽

Root Mean Square ◽

In Silico ◽

Dynamics Simulation ◽

Spike Protein ◽

Energy Calculation ◽

Mean Square ◽

Main Protease

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.

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In Silico Investigation of Spice Molecules as Potent Inhibitor of SARS-CoV-2

10.26434/chemrxiv.12323615.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Janmejaya Rout ◽

Bikash Chandra Swain ◽

Umakanta Tripathy

Keyword(s):

Infectious Disease ◽

Small Molecules ◽

Potent Inhibitor ◽

Computational Study ◽

Spike Protein ◽

Lab Experiments ◽

Main Protease ◽

Wet Lab ◽

Potential Inhibitors ◽

Adme Property

<p>The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a novel infectious disease that is in rapid growth. Several trials are going on worldwide to find a solution for this pandemic. The viral replication can be blocked by inhibiting the SARS-CoV-2 spike protein (SARS-CoV-2 Spro), and the SARS-CoV-2 main protease (SARS-CoV-2 Mpro). The binding of potential small molecules to these proteins can possibly inhibit the replication and transcription of the virus. The spice molecules that are used in our food have the properties of antiviral, antifungal, and antimicrobial nature. As spice molecules are consumed in the diet, hence its antiviral properties against SARS-CoV-2 will benefit in a significant manner. Therefore, in this work, the blind molecular docking of 30 selected spice molecules (through ADME property screening) was performed for the identification of potential inhibitors for the Spro and Mpro of SARS-CoV-2. We found that all the molecules bind actively with the SARS-CoV-2 Spro and Mpro. However, the molecule, Piperine, is found to have the highest binding affinity among the 30 screened molecules. We anticipate immediate wet-lab experiments and clinical trials in support of this computational study might be helpful in inhibiting the SARS-CoV-2 virus.</p>

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Repurposing of Anthelmintic Drugs against SARS-CoV-2 (Mpro and RdRp): Novel Disease, Older Therapeutics

Letters in Applied NanoBioScience ◽

10.33263/lianbs102.23312338 ◽

2020 ◽

Vol 10 (2) ◽

pp. 2331-2338

Keyword(s):

Antiviral Activity ◽

Protease Inhibitor ◽

In Silico ◽

Rna Polymerases ◽

The Novel ◽

Inhibitor Activity ◽

Main Protease ◽

Promising Target ◽

Potential Inhibitors ◽

Anthelmintic Drugs

Since late December 2019, the entire nations are facing the novel enemy of COVID-19, which has imposed a tremendous burden on the researchers across the globe to develop a treatment for it. Recognition of main protease and RNA dependent RNA polymerases as a promising target of SARS-CoV-2 encouraged us to repurpose some older antihelmintic drugs against COVID-19. In this constructive research, we have investigated anthelmintic drugs' antiviral activity, including ivermectin, doramectin, and selamectin, for their antiviral potential against SARS-CoV-2 by employing in silico tools. The selected drugs, including ivermectin, doramectin, and selamectin, were encountered as potential inhibitors of SARS-CoV-2 RNA-dependent RNA polymerases with an affinity of -9.2, -10.0, and -10.2 kcal/mol. They were found to exhibit main protease inhibitor activity with an affinity of -8.3, -8.7, and -9.0, respectively. Thus, using the repurposing approach in conjugation within silico tools, we have proposed ivermectin, doramectin, and selamectin as potential antivirals against SARS-CoV-2.

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