Naturally Occurring Anthraquinones as Potential Inhibitors of SARS-CoV-2 Main Protease: A Molecular Docking Study

10.26434/chemrxiv.12245270 ◽

2020 ◽

Author(s):

Sourav Das ◽

Atanu Singha Roy

Keyword(s):

Molecular Docking ◽

Drug Targets ◽

Docking Study ◽

Docking Studies ◽

World Health ◽

Molecular Docking Study ◽

Inhibitory Potential ◽

Novel Coronavirus ◽

Health Organization ◽

Potential Inhibitors

<i>Background:</i> The novel coronavirus (COVID-19) has quickly spread throughout the globe, affecting millions of people. The World Health Organization (WHO) has recently declared this infectious disease as a pandemic. At present, several clinical trials are going on to identify possible drugs for treating this infection. SARS-CoV-2 M<sup>pro</sup> is one of the most critical drug targets for the blockage of viral replication. <i>Method:</i> The blind molecular docking analyses of natural anthraquinones with SARS-CoV-2 M<sup>pro</sup> were carried out in an online server, SWISSDOCK, which is based on EADock DSS docking software. <i>Results: </i>Blind molecular docking studies indicated that several<i> </i>natural antiviral anthraquinones could prove to be effective inhibitors for SARS-CoV-2 M<sup>pro</sup> of COVID-19 as they bind near the active site having the catalytic dyad, HIS41 and CYS145 through non-covalent forces. The anthraquinones showed less inhibitory potential as compared to the FDA approved drug, remdesivir.<i></i> <p><b><i>Conclusion:</i></b><i> </i>Among the natural anthraquinones<i>, </i>alterporriol Q could be the most potential inhibitor of SARS-CoV-2 M<sup>pro</sup> among the natural anthraquinones studied here, as its ∆<i>G</i> value differed from that of remdesivir only by 0.51 kcal/ mol. The uses of these alternate compounds might be favorable for the treatment of the COVID-19.</p>

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Hispidin and Lepidine E: two Natural Compounds and Folic acid as Potential Inhibitors of 2019-novel coronavirus Main Protease (2019-nCoVMpro), molecular docking and SAR study

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200422075440 ◽

2020 ◽

Vol 16 ◽

Cited By ~ 9

Author(s):

Talia Serseg ◽

Khedidja Benarous ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Folic Acid ◽

Docking Study ◽

Natural Compounds ◽

Inhibitory Effect ◽

World Health ◽

Molecular Docking Study ◽

Main Protease ◽

Novel Coronavirus ◽

Health Organization

: 2019-nCoVis a novel coronavirus was isolated and identified in 2019 in Wuhan, China. On 17 February and according to the world health organization, a number of 71 429 confirmed cases worldwide, among them 2162 new cases recorded in the last 24 hours. One month later the confirmed cases jumped to 179111, with 11525new cases in the last 24 hours, with 7426total deaths. There is no drug or vaccine for humanand animal coronavirus.The inhibition of 3CL hydrolase enzyme provides a promising therapeutic principle for developing treatments against CoViD-19.The 3CLpro (Mpro) known for involving in counteracting the host innate immune response.Thiswork presents the inhibitory effect of some natural compounds against 3CL hydrolase enzyme, and explain the main interactions in inhibitor-enzyme complex. Molecular docking study carried out using Autodock Vina. By screening several molecules, we identified three candidate agents that inhibit the main protease of coronavirus. Hispidin, lepidine E,and folic acid bound tightly in the enzyme, strong hydrogen bonds have been formed (1.69-1.80Å) with the active site residues.This study provides a possible therapeutic strategy for CoViD-19.

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Molecular Docking Studies on the Anti-viral Effects of Compounds From Kabasura Kudineer on SARS-CoV-2 3CLpro

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.613401 ◽

2020 ◽

Vol 7 ◽

Author(s):

Savariar Vincent ◽

Selvaraj Arokiyaraj ◽

Muthupandian Saravanan ◽

Manoj Dhanraj

Keyword(s):

Molecular Docking ◽

Critical Role ◽

Drug Repurposing ◽

Docking Studies ◽

World Health ◽

Synthetic Drugs ◽

Energy Score ◽

Main Protease ◽

Novel Coronavirus ◽

Health Organization

The COVID-19 has now been declared a global pandemic by the World Health Organization. No approved drug is currently available; therefore, an urgent need has been developed for any antiviral therapy for COVID-19. Main protease 3CLpro of this novel Coronavirus (SARS-CoV-2) play a critical role in the disease propagation, and hence represent a crucial target for the drug discovery. Herein, we have applied a bioinformatics approach for drug repurposing to identify the possible potent inhibitors of SARS-CoV-2 main proteases 3CLpro (6LU7). In search of the anti-COVID-19 compound, we selected 145 phyto-compounds from Kabasura kudineer (KK), a poly-herbal formulation recommended by AYUSH for COVID-19 which are effective against fever, cough, sore throat, shortness of breath (similar to SARS-CoV2-like symptoms). The present study aims to identify molecules from natural products which may inhibit COVID-19 by acting on the main protease (3CLpro). Obtained results by molecular docking showed that Acetoside (−153.06), Luteolin 7 -rutinoside (−134.6) rutin (−133.06), Chebulagic acid (−124.3), Syrigaresinol (−120.03), Acanthoside (−122.21), Violanthin (−114.9), Andrographidine C (−101.8), myricetin (−99.96), Gingerenone -A (−93.9), Tinosporinone (−83.42), Geraniol (−62.87), Nootkatone (−62.4), Asarianin (−79.94), and Gamma sitosterol (−81.94) are main compounds from KK plants which may inhibit COVID-19 giving the better energy score compared to synthetic drugs. Based on the binding energy score, we suggest that these compounds can be tested against Coronavirus and used to develop effective antiviral drugs.

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Thiazole Based Carbohydrazide Derivatives as α-Amylase Inhibitor and Their Molecular Docking Study

Heteroatom Chemistry ◽

10.1155/2019/7502347 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Muhammad Taha ◽

Maryam Irshad ◽

Syahrul Imran ◽

Fazal Rahim ◽

Manikandan Selvaraj ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Docking Study ◽

Docking Studies ◽

Antidiabetic Agent ◽

Molecular Docking Study ◽

Binding Interaction ◽

Structure Activity ◽

Inhibitory Potential ◽

Amylase Inhibitors

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as α-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by 1HNMR, 13CNMR, and EI-MS, and evaluated for α-amylase inhibition. Except compound 11 all analogs showed α-amylase inhibitory activity with IC50 values from 1.709 ± 0.12 to 3.049 ± 0.25 μM against the standard acarbose (IC50 = 1.637 ± 0.153 μM). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with IC50 value 1.763 ± 0.03, 1.747 ± 0.20, 1.709 ± 0.12, and 1.948 ± 0.23 μM, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.

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Computational Identification of Drug Lead Compounds for COVID-19 from Moringa Oleifera

10.26434/chemrxiv.12535913.v1 ◽

2020 ◽

Author(s):

Dr. Divya Shaji

Keyword(s):

Molecular Docking ◽

Drug Targets ◽

Moringa Oleifera ◽

Docking Studies ◽

World Health ◽

Lipinski’S Rule ◽

Lead Compounds ◽

Global Pandemic ◽

Drug Lead ◽

Health Organization

<div>COVID-19 which is caused by the virus SARS-CoV-2, has now been declared a global pandemic by the World Health Organization. At present, no specific vaccines or drugs are available to treat COVID-19. Therefore, there is an urgent need for the identification of novel drug lead compounds</div><div>to treat COVID-19. The SARS-CoV-2 main protease (Mpro also known as 3CLpro) and RNA-dependent RNA polymerase (RdRp also known as nsp12) are the best-characterized drug targets among corona viruses. In order to discover the natural lead compounds for SARS-CoV-2, we</div><div>performed molecular docking with the compounds from <i>Moringa Oleifera</i> that target the Mpro and RdRp. The molecular docking studies were carried out using AutoDock Vina through PyRx. Drug-likeness property of the selected compounds was checked by applying the ‘Lipinski’s rule of five’ using Swiss ADME. The top four compounds with most favourable binding affinity were selected for each of the targets. The results indicated that the compounds kaempferol, pterygospermin, morphine and quercetin exhibited best binding energy towards Mpro and RdRp. This study suggests that these natural compounds could be promising candidates for further evaluation of COVID-19 prevention.</div>

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Computational Identification of Drug Lead Compounds for COVID-19 from Moringa Oleifera

10.26434/chemrxiv.12535913 ◽

2020 ◽

Author(s):

Dr. Divya Shaji

Keyword(s):

Molecular Docking ◽

Drug Targets ◽

Moringa Oleifera ◽

Docking Studies ◽

World Health ◽

Lipinski’S Rule ◽

Lead Compounds ◽

Global Pandemic ◽

Drug Lead ◽

Health Organization

<div>COVID-19 which is caused by the virus SARS-CoV-2, has now been declared a global pandemic by the World Health Organization. At present, no specific vaccines or drugs are available to treat COVID-19. Therefore, there is an urgent need for the identification of novel drug lead compounds</div><div>to treat COVID-19. The SARS-CoV-2 main protease (Mpro also known as 3CLpro) and RNA-dependent RNA polymerase (RdRp also known as nsp12) are the best-characterized drug targets among corona viruses. In order to discover the natural lead compounds for SARS-CoV-2, we</div><div>performed molecular docking with the compounds from <i>Moringa Oleifera</i> that target the Mpro and RdRp. The molecular docking studies were carried out using AutoDock Vina through PyRx. Drug-likeness property of the selected compounds was checked by applying the ‘Lipinski’s rule of five’ using Swiss ADME. The top four compounds with most favourable binding affinity were selected for each of the targets. The results indicated that the compounds kaempferol, pterygospermin, morphine and quercetin exhibited best binding energy towards Mpro and RdRp. This study suggests that these natural compounds could be promising candidates for further evaluation of COVID-19 prevention.</div>

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MOLECULAR DOCKING AND SCREENING OF DRUGS FOR 6LU7 PROTEASE INHIBITOR AS A POTENTIAL TARGET FOR COVID-19

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2022v14i1.43132 ◽

2022 ◽

pp. 100-105

Author(s):

MANOJ GADEWAR ◽

BHARAT LAL

Keyword(s):

Molecular Docking ◽

Data Bank ◽

Docking Study ◽

In Vivo Studies ◽

Molecular Docking Study ◽

Potential Target ◽

Novel Coronavirus ◽

Potential Inhibitors

Objective: The aim of present investigation is docking of various existing antiviral, anti-tubercular and anti-malarial drugs on 6LU7 receptor of SARS-CoV-2 in the treatment of COVID-19. Methods: In this study, the structure of coronavirus binding protein and ligands for various drugs were collected from the protein data bank and pub chem. Molecular docking was carried out using Schrodinger 9.0 software. In molecular docking study, 19 different drugs of various categories like antiviral, anti-malarial and anti-tubercular were investigated for analyzing binding to 6LU7 receptors of COVID-19. Results: The docking result showed a high affinity of zanamivir, montelukast, ramdesvir, ritonavir, cobicistat and favipravir to the 6LU7 receptor of novel coronavirus. Thus the combination of these drugs may be useful in preventing further infection and can be used as a potential target for further in vitro and in vivo studies of SARS-CoV-2. Conclusion: Treatment of COVID-19 has been challenge due to the non-availability of effective drug therapy. In this study, we reported drugs for targeting 6LU7 Mpro/3Clpro protein, which showed prominent effects as potential inhibitors of COVID-19 Mpro.

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Interaction between DNA, Albumin and Apo-Transferrin and Iridium(III) Complexes with Phosphines Derived from Fluoroquinolones as a Potent Anticancer Drug

Pharmaceuticals ◽

10.3390/ph14070685 ◽

2021 ◽

Vol 14 (7) ◽

pp. 685

Author(s):

Sandra Amanda Kozieł ◽

Monika Katarzyna Lesiów ◽

Daria Wojtala ◽

Edyta Dyguda-Kazimierowicz ◽

Dariusz Bieńko ◽

...

Keyword(s):

Molecular Docking ◽

Serum Proteins ◽

Docking Study ◽

Minor Groove ◽

Docking Studies ◽

Minor Groove Binding ◽

Binding Modes ◽

Groove Binding ◽

Molecular Docking Study ◽

Threading Intercalation

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage. The molecular docking study confirmed two binding modes: minor groove binding and threading intercalation with the fluoroquinolone part of the molecule involved in pi stacking interactions and the Ir(III)-containing region positioned within the major or minor groove. Fluorescence spectroscopic data (HSA and apo-Tf titration), together with molecular docking, provided evidence that Ir(III) complexes can bind to the proteins in order to be transferred. All the compounds considered herein were found to bind to the tryptophan residues of HSA within site I (subdomain II A). Furthermore, Ir(III) complexes were found to dock within the apo-Tf binding site, including nearby tyrosine residues.

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Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

Physical Sciences Reviews ◽

10.1515/psr-2019-0136 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Joshua Oluwasegun Bamidele ◽

George Oche Ambrose ◽

Oluwaseun Suleiman Alakanse

Keyword(s):

Molecular Docking ◽

Liver Toxicity ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Docking Analysis ◽

Computational Docking ◽

Drug Candidates ◽

Expression Rate ◽

Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

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