In Silico Screening of Potent Bioactive Compounds from Honey Bee Products Against COVID-19 Target Enzymes

From the early days of the COVID-19 pandemic, side by side to immense investigates to design specific drugs or to develop a potential vaccine for the novel coronavirus. Myriads of FDA approved drugs are massively repurposed for COVID-19 treatment based on molecular docking of selected protein targets that play vital for the replication cycle of the virus. Honey bee products are well known of their nutritional values and medicinal effects. Antimicrobial activity of bee products and natural honey have been documented in several clinical studies and was considered a good alternative for antiviral medications to treat some viral infections. Bee products contain bioactive compounds in the form of a collection of phenolic acids, flavonoids and terpenes of natural origin. We revealed by molecular docking the profound binding affinity of 14 selected phenolics and terpenes present in honey and propolis (bees glue) against the main protease (M<sup>pro</sup>) and RNA dependent RNA polymerase (RdRp) enzymes of the novel 2019-nCoV coronavirus. Of these compounds, <i>p</i>-coumaric acid, ellagic acid, kaemferol and quercetin has the strongest interaction with the 2019-nCoV target enzymes, and they may be considered as an effective 2019-nCoV inhibitors.

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Therapeutics targeting the main protease of SARS-CoV-2 for the treatment of COVID-19: A molecular modeling approach deciphering relative efficacies

10.21203/rs.3.rs-110749/v1 ◽

2020 ◽

Author(s):

Shuvasish Choudhury ◽

Purbajyoti Saikia ◽

Debojyoti Moulick ◽

Muhammed Khairujjaman Mazumder

Keyword(s):

Molecular Docking ◽

Molecular Modeling ◽

Protease Inhibitors ◽

Drug Target ◽

De Novo ◽

The Novel ◽

Main Protease ◽

Docking Tool ◽

Novel Coronavirus ◽

Approved Drugs

Abstract The pandemic due to the novel coronavirus 2019, SARS-CoV-2, has led to a global health and economic crisis. The disease, named coronavirus disease (COVID-19), has already affected 3090445 and killed over 217769 people worldwide, as of April 30, 2020. So far, there is no specific effective medicine or vaccine against SARS-CoV-2. Several existing and approved drugs are under clinical studies for re-purposing. However, owing to the emergent situation and thereby to avoid time needed for de novo drug discovery, drug re-purposing remains to be the best option to find an effective therapeutic against the virus. Thus, the preset study was designed to evaluate potency of 82 compound/drugs in inhibiting the main protease (3CLPro) of SARS-CoV-2, using molecular docking tool. This protease is a vital enzyme for replication of the virus, and is thus a promising drug target. The analyzed compounds include 16 known protease inhibitors, two recently suggested α-ketoamides, 24 recently reported putative inhibitors, and 40 phytochemicals. The results indicate that Ritonavir, Indinavir, Montelukast, Nelfinavir, Candoxatril, Tigecycline and Lopinavir to be very potent protease inhibitors. Further, several other drugs and compounds, including phytochemicals, have been identified / predicted to be potent in inhibiting the enzyme. In addition, we hereby report relative efficacies of these compounds in inhibiting 3CLPro. Thus, the present study is significant in the therapeutic intervention of COVID-19.

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

BioTechniques ◽

10.2144/btn-2020-0038 ◽

2020 ◽

Vol 69 (2) ◽

pp. 108-112 ◽

Cited By ~ 1

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.

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Screening of Kabasura Kudineer Chooranam against COVID-19 through Targeting of Main Protease and RNA-Dependent RNA Polymerase of SARS-CoV-2 by Molecular Docking Studies

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2020.ajomc-p299 ◽

2020 ◽

Vol 5 (4) ◽

pp. 319-331

Author(s):

K. Gopalasatheeskumar ◽

Karthikeyen Lakshmanan ◽

Anguraj Moulishankar ◽

Jerad Suresh ◽

D. Kumuthaveni Babu ◽

...

Keyword(s):

Molecular Docking ◽

Rna Polymerase ◽

Docking Studies ◽

The Novel ◽

Rna Dependent Rna Polymerase ◽

Molecular Docking Studies ◽

Main Protease ◽

Short Span ◽

Novel Coronavirus

COVID-19 is the infectious pandemic disease caused by the novel coronavirus. The COVID-19 is spread globally in a short span of time. The Ministry of AYUSH, India which promotes Siddha and other Indian system of medicine recommends the use of formulation like Nilavembu Kudineer and Kaba Sura Kudineer Chooranam (KSKC). The present work seeks to provide the evidence for the action of 74 different constituents of the KSKC formulation acting on two critical targets. That is main protease and SARS-CoV-2 RNAdependent RNA polymerase target through molecular docking studies. The molecular docking was done by using AutoDock Tools 1.5.6 of the 74 compounds, about 50 compounds yielded docking results against COVID-19 main protease while 42 compounds yielded against SARSCoV- 2 RNA-dependent RNA polymerase. This research has concluded that the KSKC has the lead molecules that inhibits COVID-19’s target of main protease of COVID-19 and SARS-CoV-2 RNA-dependent RNA polymerase.

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Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus

Bioinformation ◽

10.6026/97320630016236 ◽

2020 ◽

Vol 16 (3) ◽

pp. 236-244 ◽

Cited By ~ 16

Author(s):

Hasanain Abdulhameed Odhar ◽

Keyword(s):

Molecular Docking ◽

Dynamics Simulation ◽

Main Protease ◽

Novel Coronavirus ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Molecular Docking And Dynamics

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In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

10.26434/chemrxiv.12049590.v1 ◽

2020 ◽

Cited By ~ 3

Author(s):

Yogesh Kumar ◽

Harvijay Singh

Keyword(s):

Virtual Screening ◽

Active Site ◽

Viral Infections ◽

Drug Repurposing ◽

Docking Study ◽

Docking Studies ◽

Main Protease ◽

Novel Coronavirus ◽

Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

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In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

10.26434/chemrxiv.12049590 ◽

2020 ◽

Cited By ~ 1

Author(s):

Yogesh Kumar ◽

Harvijay Singh

Keyword(s):

Virtual Screening ◽

Active Site ◽

Viral Infections ◽

Drug Repurposing ◽

Docking Study ◽

Docking Studies ◽

Main Protease ◽

Novel Coronavirus ◽

Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

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Computational studies by molecular docking of some antiviral drugs with COVID-19 receptors are an approach to medication for COVID-19

Open Chemistry ◽

10.1515/chem-2021-0024 ◽

2021 ◽

Vol 19 (1) ◽

pp. 245-264

Author(s):

Magda H. Abdellatiif ◽

Amena Ali ◽

Abuzer Ali ◽

Mostafa A. Hussien

Keyword(s):

Molecular Docking ◽

Antiviral Drug ◽

Chemotherapeutic Agents ◽

The Novel ◽

Drug Molecules ◽

Study Results ◽

Promising Treatment ◽

Novel Coronavirus ◽

Approved Drugs ◽

Fda Approved Drugs

Abstract The COVID-19 outbreak is a matter of concern worldwide due to unavailability of promising treatment comprising medication or vaccination till date. The discovery of antiviral drug is of immense importance in the existing spread of novel coronavirus. The goal of the present study was to evolve an opposite antiviral drug against the novel COVID-19 virus. A directly succeeding perspective would be to use the prevailing influential drugs from several antimicrobial and chemotherapeutic agents. The encouraging approach is to identify promising drug molecules and compounds through virtual screening via molecular docking of FDA-approved drugs and some previously synthesized pyridone and coumarin derivatives for probable therapeutic outcome. In this conceptual milieu, an effort has been made to propose a computational in silico relationship among FDA-approved drugs and coronavirus-associated receptors and proteins. The study results were evaluated on the basis of a dock score by using molecular operating environment. Out of 15 compounds screened, the compounds with the best docking scores toward their targets was 3d. Therefore, compound 3d deserves further investigations and clinical trials as a possible therapeutic inhibitor of the COVID-19 caused by the novel SARS-CoV-2.

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In Silico Identification of Potent COVID-19 Main Protease Inhibitors from FDA Approved Antiviral Compounds and Active Phytochemicals through Molecular Docking: A Drug Repurposing Approach

10.20944/preprints202003.0349.v1 ◽

2020 ◽

Cited By ~ 2

Author(s):

Vaishali Chandel ◽

Sibi Raj ◽

Brijesh Rathi ◽

Dhruv Kumar

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Binding Affinity ◽

Drug Repurposing ◽

The Novel ◽

Antiviral Compounds ◽

Ssrna Virus ◽

Main Protease ◽

Adme Properties ◽

Novel Coronavirus

The Novel Coronavirus (COVID-19) is a positive-sense single-stranded RNA ((+)ssRNA) virus. The COVID-19 Main Proteases play very important role in the propagation of the Novel Coronavirus (COVID-19). It has already killed more than 8000 people around the world and thousands of people are getting infected every day. Therefore, it is very important to identify a potential inhibitor against COVID-19 Main Proteases to inhibit the propagation of the Novel Coronavirus (COVID-19). We have applied a drug repurposing approach of computational methodology, depending on the synergy of molecular docking and virtual screening techniques, aimed to identify possible potent inhibitors against Novel Coronavirus (COVID-19) from FDA approved antiviral compounds and from the library of active phytochemicals. On the basis of recently resolved COVID-19 Main Protease crystal structure (PDB:6LU7), the library of 100 FDA approved antiviral compounds and 1000 active components of Indian Medicinal Plants extracted for screening against COVID-19 Main Protease. The compounds were further screened using Pyrex virtual screening tool and then best inhibitors, top 19 compounds optimally docked to the COVID-19 Main Protease structure to understand the participation of specific amino acids with inhibitors at active sites. Total 19 best compounds were identified after screening based on their highest binding affinity with respect to the other screened compounds. Out of 19, 6 best compounds were further screened based on their binding affinity and best ADME properties. Nelfinavir exhibited highest binding energy -8.4 kcal/mol and strong stability with the TRP207, ILE281, LEU282, PHE3, PHE291, GLN127, ARG4, GLY283, GLU288, LYS5, LYS137, TYR126, GLY138, TYR126, SER139 and VAL135 amino acid residues of COVID-19 Main Protease participating in the interaction at the binding pocket. In addition to Nelfinavir (-8.4), Rhein (-8.1), Withanolide D (-7.8), Withaferin A (-7.7), Enoxacin (-7.4), and Aloe-emodin (-7.4) also showed good binding affinity and best ADME properties. Our findings suggest that these compounds can be used as potential inhibitors against COVID-19 Main Protease, which could be helpful in inhibiting the propagation of the Novel Coronavirus (COVID-19). Moreover, further in vitro and in vivo validation of these findings would be very helpful to bring these inhibitors to next level study.

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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 <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.

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