scholarly journals Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1257
Author(s):  
Fareena Shahid ◽  
Noreen ◽  
Roshan Ali ◽  
Syed Lal Badshah ◽  
Syed Babar Jamal ◽  
...  
Keyword(s):  
Hepatitis C ◽  
In Silico ◽  
Experimental Validation ◽  
Homology Modelling ◽  
Viral Envelope ◽  
Screening Methods ◽  
Binding Affinities ◽  
Autodock Vina ◽  
Potential Inhibitors ◽  
Very High

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

scholarly journals In Silico Screening for Natural Ligands to Non-Structural Nsp7 Conformers of Coronaviruses

2020 ◽  
Author(s):  
Rafael Blasco ◽  
Julio Coll
Keyword(s):  
In Silico ◽  
Chemical Properties ◽  
Structural Similarity ◽  
Binding Pocket ◽  
Binding Affinities ◽  
Structural Protein ◽  
Autodock Vina ◽  
Natural Ligands ◽  
Final Optimization

<p>The non-structural protein 7 (nsp7) of Severe Acute Respiratory Syndrome (SARS) coronaviruses was selected as a new target to potentially interfere with viral replication. The nsp7s are one of the most conserved, unique and small coronavirus proteins having a critical, yet intriguing participation on the replication of the long viral RNA genome after complexing with nsp8 and nsp12. Despite the difficulties of having no previous binding pocket, two high-throughput virtual blind screening of 158240 natural compounds > 400 Da by AutoDock Vina against nsp7.1ysy identified 655 leads displaying predicted binding affinities between 10 to 1100 nM. The leads were then screened against 14 available conformations of nsp7 by both AutoDock Vina and seeSAR programs employing different binding score algorithms, to identify 20 consensus top-leads. Further <i>in silico</i> predictive analysis of physiological and toxicity ADMET criteria (chemical properties, adsorption, metabolism, toxicity) narrowed top-leads to a few drug-like ligands many of them showing steroid-like structures. A final optimization by search for structural similarity to the top drug-like ligand that were also commercially available, yielded a collection of predicted novel ligands with ~100-fold higher-affinity whose antiviral activity may be experimentally validated. Additionally, these novel nsp7-interacting ligands and/or their further optimized derivatives, may offer new tools to investigate the intriguing role of nsp7 on replication of coronaviruses.</p>

scholarly journals Triple Targeting of Human IMPDH and Both RdRps of SARS-CoV-2 and Rhizopus Oryzae: An in Silico Perspective

2021 ◽  
Author(s):  
Abdel_moniem S Hassan ◽  
Abdo A Elfiky ◽  
Alaa Elgohary
Keyword(s):  
In Silico ◽  
Fungal Pathogens ◽  
Experimental Validation ◽  
Rhizopus Oryzae ◽  
Dynamics Simulation ◽  
Binding Affinities ◽  
Inosine Monophosphate Dehydrogenase ◽  
Rna Dependent Rna Polymerase ◽  
Protein Target ◽  
The Past

Abstract Mucormycosis has been reported in many regions associated with SARS-CoV-2 infections during the past few months. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target in viral and fungal pathogens. Molecular docking combined with molecular dynamics simulation (MDS) is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. Additionally, the human Inosine monophosphate dehydrogenase (IMPDH) was targeted by the same inhibitors. The results reveal a comparable binding affinity of four nucleotide derivatives compared to remdesivir and sofosbuvir against both IMPDH and the RdRps of SARS-CoV-2 and Rhizopus oryzae, the main causing agent of mucormycosis. The binding affinities are calculated using different conformations of the RdRps after 100 ns MDS and trajectories clustering. The present study suggests the triple inhibition potential of four nucleotide inhibitors against SARS-CoV-2 & R. oryzae RdRps and the human IMPDH, while experimental validation is yet to be performed.

scholarly journals Evaluation of Phytochemicals of Cassia occidentalis L. for their Binding Affinities to SARS-CoV-2 3C-Like Protease: An in Silico Approach

2020 ◽  
pp. 8-14
Author(s):  
Tohmina Afroze Bondhon ◽  
Md. Aynal Haque Rana ◽  
Anamul Hasan ◽  
Rownak Jahan ◽  
Khoshnur Jannat ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Binding Affinities ◽  
Autodock Vina ◽  
Cassia Occidentalis ◽  
Main Protease ◽  
In Silico Studies ◽  
The World ◽  
Docking Approach

Aims: Corona virus SARS-CoV-2, otherwise known as COVID-19 has created a pandemic resulting in social and financial crisis throughout the world. The virus has no known drugs or vaccines for preventive or therapeutic purposes. The objective of the present study was to screen phytochemicals from Cassia occidentalis L. in virtual screening (in silico) studies to evaluate their potential of binding to the main 3C-like protease of the virus and so stop its replication. Study Design: Molecular docking approach was used for virtual screening studies. Place and Duration of Study: University of Development Alternative between April and July 2020. Methodology: Molecular docking (blind) were done with the help of Autodock Vina. We have used the pdb file (6LU7) of the main protease of SARS-CoV-2 3C-like protease or SARS-CoV-2 3CLpro (monomeric form) to study binding of the phytochemicals. Results: Of the nine phytochemicals studied, the C-glycosidic flavonoids, cassiaoccidentalins A-C demonstrated excellent binding affinities to the protease. The compounds bound to the active site of the protease with binding energy values of -8.2 to-8.4 kcal/mol. Conclusion: The in silico studies suggest that the compounds merit actual COVID-19 inhibitory tests and have potential for anti-COVID-19 use.

The antiviral Sofosbuvir against mucormycosis: an in silico perspective

2019 ◽  
Vol 14 (11) ◽  
pp. 739-744 ◽  
Author(s):  
Abdo A Elfiky
Keyword(s):  
Homology Modeling ◽  
In Silico ◽  
Viral Infections ◽  
Rhizopus Oryzae ◽  
Polymerization Process ◽  
Binding Affinities ◽  
Autodock Vina ◽  
Rna Dependent Rna Polymerase ◽  
Protein Target ◽  
Rna Polymerization

Aim: Mucormycosis (zygomycosis) is a rare fungal infection that affects humans (40–100% mortality). Rhizopus oryzae is the primary fungus responsible for 70% of mucormycosis cases. RNA-dependent RNA polymerase (RdRp) is a vital enzyme accountable for the RNA polymerization process in different organisms, including R. oryzae. Blocking this enzyme has been previously reported as a successful strategy to eradicate viral infections. Materials & methods: AutoDock Vina is utilized for the calculation of binding affinities of Sofosbuvir, Ribavirin and uridine triphosphate nucleotide to the fungal RdRp model built by homology modeling (no solved structures available). Results: Sofosbuvir shows excellent binding affinity to the fungal RdRp in silico. Conclusion: In this study, R. oryzae RdRp is suggested to be a possible protein target against the nucleotide inhibitor, Sofosbuvir.

In silico identification of potential inhibitors of SARS-CoV-2 papain-like protease from natural sources: A natural weapon to fight COVID-19

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Bimal Debnath ◽  
Pradip Debnath ◽  
Rajat Ghosh ◽  
Sudhan Debnath
Keyword(s):  
In Silico ◽  
Curcuma Longa ◽  
Homology Modelling ◽  
In Vitro Study ◽  
Mentha Piperita ◽  
In Silico Identification ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Critical Regions

Background:: The rapid spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) globally has created unprecedented health care and economic crisis. The ever-increasing death toll highlights an urgent need for the development of specific antiviral to combat Novel Coronavirus Disease 2019 (COVID-19). Objective:: In the present study we aim to identify potential SARS-CoV-2 papain-like protease inhibitors from regularly used spices. Methods:: A structure-based virtual screening (VS) of our in-house databank of 1152 compounds was employed to identify small molecule inhibitors of SARS-CoV-2 papain-like protease (PLpro), which are important protease for virus replication. The databank was built of the compounds from ten spices and two medicinal plants. Results:: The top three potential hits resulted from VS were myricetin (1) available in Alium cepa, Mentha piperita, α- hydroxyhydrocaffeic acid (2) available in M. Piperita and luteolin (3) available in M. Piperita, Curcuma longa, A. cepa, Trigonella foenum-graecum which showed fair binding affinity to PLpro of SARS-CoV-2 compared to known SARS-CoV PLpro inhibitors. The predicted Absorption, Distribution, Metabolism, and Excretion (ADME) properties of the selected hits showed that all are drug like. The compounds bind to biologically critical regions of the target protein, indicating their potential to inhibit the functionality of this component. Conclusion:: There are only a few reports available in the literature on the in-silico identification of PLpro inhibitors and most of them used homology modelling of protein. Here, we used the recently uploaded X-ray crystal structure of PLpro (PDB ID: 6WX4) with the well-defined active site. Our computational approach has resulted in the identification of effective inhibitors of SARS-CoV-2PLpro. The reported edible spices may be useful against COVID-19 as home remedy after in-vitro study.

scholarly journals In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159211 ◽  
Author(s):  
Mahmoud ElHefnawi ◽  
TaeKyu Kim ◽  
Mona A. Kamar ◽  
Saehong Min ◽  
Nafisa M. Hassan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Silico ◽  
Experimental Validation ◽  
In Silico Design ◽  
Conserved Regions ◽  
Virus Genotypes ◽  
Hepatitis C Virus Genotypes

scholarly journals In silico drug repurposing for filarial infection predicts nilotinib and paritaprevir as potential inhibitors of the Wolbachia 5′-aminolevulinic acid synthase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Kwarteng ◽  
Ebenezer Asiedu ◽  
Augustina Sylverken ◽  
Amma Larbi ◽  
Yusif Mubarik ◽  
...  
Keyword(s):  
In Silico ◽  
Aminolevulinic Acid ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Clinical Effectiveness ◽  
Current Treatment ◽  
Binding Affinities ◽  
Active Site Residues ◽  
Experimental Validations ◽  
Potential Inhibitors

AbstractFilarial infections affect millions of individuals and are responsible for some notorious disabilities. Current treatment options involve repeated mass drug administrations, which have been met with several challenges despite some successes. Administration of doxycycline, an anti-Wolbachia agent, has shown clinical effectiveness but has several limitations, including long treatment durations and contraindications. We describe the use of an in silico drug repurposing approach to screening a library of over 3200 FDA-approved medications against the filarial endosymbiont, Wolbachia. We target the enzyme which catalyzes the first step of heme biosynthesis in the Wolbachia. This presents an opportunity to inhibit heme synthesis, which leads to depriving the filarial worm of heme, resulting in a subsequent macrofilaricidal effect. High throughput virtual screening, molecular docking and molecular simulations with binding energy calculations led to the identification of paritaprevir and nilotinib as potential anti-Wolbachia agents. Having higher binding affinities to the catalytic pocket than the natural substrate, these drugs have the structural potential to bind and engage active site residues of the wolbachia 5′-Aminolevulinic Acid Synthase. We hereby propose paritaprevir and nilotinib for experimental validations as anti-Wolbachia agents.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

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