scholarly journals Novel Coronavirus (SARS-CoV-2) Main Protease: Molecular docking of Puerarin as a Potential inhibitor

2020 ◽  
Author(s):  
Oluwafemi Adeleke Ojo ◽  
Adebola Busola Ojo ◽  
Odunayo Anthonia Taiwo ◽  
Olarewaju M Oluba
Keyword(s):  
Molecular Docking ◽  
Rna Virus ◽  
Drug Candidate ◽  
Lipinski’S Rule ◽  
Global Pandemic ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Novel Coronavirus ◽  
Research World ◽  
High Binding Affinity

Abstract SARS-CoV-2 a single stranded RNA virus which triggered the global pandemic Coronavirus Disease- 2019 (COVID-2019). It has infected about 2,844,712 patients and brought forth mortality rate to about 201,315 among 216 countries as cited by WHO. Drugs including Chloroquine and Hydroxychloroquine derivatives are being administered in most urgent cases; although, with probable side effects to people with metabolic disorders. Thus, unavailability of authorized drugs and treatment for this pandemic demands the research world to discover natural compounds with potency to cure it. This paper assesses the isoflavonoid puerarin from Pueraria lobata as a possible inhibitor of the main protease of SARS-COV-2 (Mpro) via in silico approach, for example molecular docking, Lipinski’s rule of five and toxicity prediction (ADME). Puerarin revealed high binding affinity with the target site of SARS-CoV-2 main protease. This compound slightly meets the criteria of Lipinski’s rule and does not possess properties that could cause adverse effects in humans thus, making puerarin a potential drug candidate to investigate for its usage against COVID-19.

scholarly journals Molecular Docking and Molecular Dynamics Aided Virtual Search of OliveNet™ Directory for Secoiridoids to Combat SARS-CoV-2 Infection and Associated Hyperinflammatory Responses

2021 ◽  
Vol 7 ◽  
Author(s):  
Neelaveni Thangavel ◽  
Mohammad Al Bratty ◽  
Hassan Ahmad Al Hazmi ◽  
Asim Najmi ◽  
Reem Othman Ali Alaqi
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Oral Absorption ◽  
Olive Tree ◽  
Viral Disease ◽  
S Protein ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
The Moment

Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified potential secoiridoids that combat SARS-CoV-2 entry, replication, and associated hyperinflammatory responses. OliveNet™ is an active directory of phytochemicals obtained from different parts of the olive tree, Olea europaea (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Secoiridoids is the largest group of olive phenols and is exclusive to the olive fruits. Functional food like olive fruits could help prevent and alleviate viral disease at an affordable cost. A systematized virtual search of 932 conformers of 78 secoiridoids utilizing Autodock Vina, followed by precision docking using Idock and Smina indicated that Nüzhenide oleoside (NZO), Oleuropein dimer (OED), and Dihydro oleuropein (DHO) blocked the SARS-CoV-2 spike (S) protein-ACE-2 interface; Demethyloleuropein (DMO), Neo-nüzhenide (NNZ), and Nüzhenide (NZE) blocked the SARS-CoV-2 main protease (Mpro). Molecular dynamics (MD) simulation of the NZO-S-protein-ACE-2 complex by Desmond revealed stability during 50 ns. RMSD of the NZO-S-protein-ACE-2 complex converged at 2.1 Å after 20 ns. During MD, the interaction fractions confirmed multiple interactions of NZO with Lys417, a crucial residue for inhibition of S protein. MD of DMO-Mpro complex proved its stability as the RMSD converged at 1.6 Å. Analysis of interactions during MD confirmed the interaction of Cys145 of Mpro with DMO and, thus, its inhibition. The docking predicted IC50 of NZO and DMO was 11.58 and 6.44 μM, respectively. Molecular docking and dynamics of inhibition of the S protein and Mpro by NZO and DMO correlated well. Docking of the six-hit secoiridoids to IL1R, IL6R, and TNFR1, the receptors of inflammatory cytokines IL1β, IL6, and TNFα, revealed the anti-inflammatory potential except for DHO. Due to intricate structures, the secoiridoids violated Lipinski's rule of five. However, the drug scores of secoiridoids supported their use as drugs. The ADMET predictions implied that the secoiridoids are non-toxic and pose low oral absorption. Secoiridoids need further optimization and are a suitable lead for the discovery of anti-SARS-CoV-2 therapeutics. For the moment, olive secoiridoids presents an accessible mode of prevention and therapy of SARS-CoV-2 infection.

scholarly journals Interactions of Alkyl Gallates with SARS-CoV-2 Main Protease: A Molecular Docking Approach

2020 ◽  
Vol 3 (1) ◽  
pp. 9
Author(s):  
Amalia Stefaniu ◽  
Lucia Pintilie ◽  
Bujor Albu ◽  
Lucia Pirvu
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Synthetic Compounds ◽  
X Ray ◽  
Lipinski’S Rule ◽  
Alkyl Gallates ◽  
Main Protease ◽  
Docking Approach ◽  
Lipinski’S Rule Of Five ◽  
In Silico Methods

Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in silico methods in order to evaluate their potential inhibitory activity against SAR-CoV-2 using the X-ray structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 Å (PDB ID: 6WNP). The evaluation of drug-likeness in terms of Lipinski’s Rule of Five and docking results in terms of docking score and interactions with the amino acids residues from the active binding site of the target protein were reported.

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

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.

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

2020 ◽  
Author(s):  
Shravan Kumar Gunda ◽  
Hima Kumari P ◽  
Gourav Choudhir ◽  
Anuj Kumar ◽  
P B. Kavi Kishor ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Dynamics Simulations ◽  
Potential Inhibitors

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.

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

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.

scholarly journals 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

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 <i>Solanum trilobatum</i> Linn. such as Solanidine, Solasodine and <i>a</i>–Solanine as potential inhibitors against the main protease (M<sup>pro</sup>) 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 M<sup>pro</sup>. 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.

scholarly journals 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

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 <i>Solanum trilobatum</i> Linn. such as Solanidine, Solasodine and <i>a</i>–Solanine as potential inhibitors against the main protease (M<sup>pro</sup>) 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 M<sup>pro</sup>. 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.

scholarly journals 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

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 <i>Solanum trilobatum</i> Linn. such as Solanidine, Solasodine and <i>a</i>–Solanine as potential inhibitors against the main protease (M<sup>pro</sup>) 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 M<sup>pro</sup>. 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.

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

2021 ◽  
Author(s):  
Shravan Kumar Gunda ◽  
Hima Kumari P ◽  
Anuj Kumar ◽  
P B. Kavi Kishor ◽  
Anil Kumar S
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Dynamics Simulations ◽  
Potential Inhibitors

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.

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