Molecular docking and Pharmacoinformatics studies reveal potential phytochemicals against HCV NS5B Polymerase

2020 ◽  
Vol 23 ◽  
Author(s):  
Hina Khalid ◽  
Usman Ali Ashfaq
Keyword(s):  
Molecular Docking ◽  
Computational Study ◽  
Health Issues ◽  
Reference Drug ◽  
Antiviral Compounds ◽  
Alternative Approach ◽  
Study Results ◽  
Docking Approach ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

: Background: Hepatitis C Virus (HCV) is one of the serious health issues affecting one-third of the world’s population. The high variations of the HCV genome are ascribed to quick replication by NS5B Polymerase and are thus the most attractive target for developing anti-HCV agents. Objective: The current study aimed to discover novel phytochemicals that harbor the potential of NS5B polymerase inhibition. Method: In this computational study, a molecular docking approach was used to screen phytochemicals with the best binding and spatial affinity with NS5B at the Palm I region. The top-ranked compounds were then subjected to in-silico pharmacokinetic and toxicological study. Results and Conclusion: The virtual screening provided seven ‘hit compounds’ including Betanin, 3,5'- dihydroxythalifaboramine, Diarctigenin, 6'-desmethylthalifaboramine, Cephalotaxine, 5alpha-O-(3'-dimethylamino-3'- phenylpropionyl) taxinine M and IsoTetrandrine with minimum binding score compared to the reference drug, Sofosbuvir (−14.7 kcal/mol). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and thorough toxicological analysis revealed a favorable and the safety profile of these compounds. The study would demonstrate the phytochemicals identified might serve as potential antiviral compounds that can potentially an alternative approach for amelioration of HCV

Repositioning of RdRp Inhibitors against HCV NS5B Polymerase Utilizing Structure-Based Molecular Docking

2021 ◽  
Vol 24 ◽  
Author(s):  
Heena Tarannum ◽  
Sisir Nandi
Keyword(s):  
Molecular Docking ◽  
Hepatitis C ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Docking Simulation ◽  
World Health ◽  
Reference Drug ◽  
The World ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

Objective: Hepatitis C Virus (HCV) is very dreadful as it can attack an estimated 71 million people around the world. The World Health Organization (WHO) reported that every year about 399000 people die due to HCV caused by chronic cirrhosis and liver cancer globally. There are many drugs available for the treatment of HCV. But drug resistance and toxicity are major issues. The quest for potential drugs utilizing repositioning would be a very useful and economical method to combat the HCV. Methods: One of the most HCV targets is RNA dependent RNA polymerase (RdRp). The RdRp is common in HCV, Dengue virus (DENV), Zika virus (ZIKV), and Yellow fever virus (YFV) belonging to the same family of Flaviviridae. An attempt has been made in the present study to repositioning different DENV, ZIKV, and YFV RdRp inhibitors against HCV NS5B polymerase utilizing structure-based molecular docking which explores the affinity and mode of binding of these RdRp inhibitors. Results: Several 87 compounds having dengue, yellow fever and zika RdRp inhibitory activities have been taken into consideration for the screening of potential RdRp leads utilizing docking simulation which focuses the affinity and mode of binding of sofosbuvir diphosphate which is a standard HCV, RdRp inhibitor. Conclusion: It was found that the compounds 6 (N-sulfonylanthranilic acid derivative), 17 (R1479), 20 (DMB220), 23 (FD-83-KI26), 40 (CCG-7648), 50 (T-1106), 65 (mycophenolic acid), and 69 (DMB213) can produce docking score with the range of -7.602 to -8.971 Kcal/Mol having almost same mode of interaction as compared to the reference drug molecule. The drugs mentioned above can produce satisfactory affinity to bind the hepatitis C viral RdRp and thus may be used to treat the disease. Therefore, these predicted compounds may be potential leads for further testing of anti HCV activity and can be repurposed to combat HCV. The high throughput shotgun of drug repurposing utilizing structure-based docking simulation freeware would be a cost-effective way to screen the potential anti-HCV leads.

QSAR and Molecular Docking Directed Synthesis and Preliminary Evaluation of Novel Non-Nucleoside HCV NS5B Polymerase Inhibitors

2017 ◽  
Vol 15 (1) ◽  
pp. 52-56
Author(s):  
Vaishali M. Patil ◽  
Neeraj Masand ◽  
Gurukumar K. R ◽  
Maksim Chudayeu ◽  
Satya Prakash Gupta ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Preliminary Evaluation ◽  
Polymerase Inhibitors ◽  
Directed Synthesis ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

scholarly journals Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 673
Author(s):  
Riadh Badraoui ◽  
Mohd Adnan ◽  
Fevzi Bardakci ◽  
Mousa M. Alreshidi
Keyword(s):  
Molecular Docking ◽  
Computational Study ◽  
Management Strategies ◽  
Protein A ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Disease Pathogenesis ◽  
Docking Approach ◽  
Coding Variants ◽  
The Relationship

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 × 10−3 to 5.47 × 10−6 for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.

Novel Guanosine Derivatives as Anti-HCV NS5b Polymerase: A QSAR and Molecular Docking Study

2019 ◽  
Vol 15 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Abdo A. Elfiky
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Active Site ◽  
Docking Study ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Docking Calculations ◽  
Quantitative Structure Activity Relationships ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

Background: IDX-184 is a guanosine derivative having a potent inhibitory performance against HCV NS5b polymerase. Objective: To test three different groups of 2'C - modified analogues of guanosine nucleotide against HCV polymerase. Method: Using combined Quantitative Structure-Activity Relationships (QSAR) and molecular docking, the suggested compounds are studied. Results: Examining the docked structures of the compounds with experimentally solved NS5b structure (PDB ID: 2XI3) revealed that most of the compounds have the same mode of interaction as that of guanosine nucleotide and hence, NS5b inhibition is possible. Conclusion: It is revealed that sixteen modifications have a better binding affinity to NS5b compared to guanosine. In addition, seven more compounds are better in NS5b binding compared to the approved drug, sofosbuvir, and the compound under clinical trials, IDX-184. Hence, these compounds could be potent HCV NS5b inhibitors. Summary Points: Novel guanosine modifications were introduced in silico and optimized using QM. QSAR and docking calculations are performed to test the binding affinity of the compounds to HCV NS5b active site. Comparison between the binding affinities and the mode of interactions of the compounds and both GTP and IDX-184 is performed. Structural mining to quantify the mode of binding of the compounds to NS5b active site pocket.

scholarly journals Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study

2020 ◽  
Vol 19 ◽  
pp. 100345 ◽  
Author(s):  
K. Abraham Peele ◽  
Chandrasai Potla Durthi ◽  
T. Srihansa ◽  
S. Krupanidhi ◽  
Vijaya Sai Ayyagari ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Computational Study ◽  
Dynamic Simulations ◽  
Antiviral Compounds

scholarly journals Combination of pharmacophore hypothesis and molecular docking to identify novel inhibitors of HCV NS5B polymerase

2015 ◽  
Vol 19 (3) ◽  
pp. 529-539 ◽  
Author(s):  
Amaravadhi Harikishore ◽  
Enlin Li ◽  
Jia Jun Lee ◽  
Nam-Joon Cho ◽  
Ho Sup Yoon
Keyword(s):  
Molecular Docking ◽  
Pharmacophore Hypothesis ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

Combined 3D-QSAR, molecular docking and molecular dynamics study on the benzimidazole inhibitors targeting HCV NS5B polymerase

2019 ◽  
Vol 38 (4) ◽  
pp. 1071-1082 ◽  
Author(s):  
Zhiguo Wang ◽  
Zhenming Chen ◽  
Jianfeng Li ◽  
Jing Huang ◽  
Chenni Zheng ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
3D Qsar ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

scholarly journals Molecular Study of Antiviral Compound of Indonesian Herbal Medicine as 3CLpro and PLpro Inhibitor in SARS-COV-2

2021 ◽  
Vol 4 (2) ◽  
pp. 127-134
Author(s):  
Baiq Ressa Puspita Rizma ◽  
Yek Zen Mubarok ◽  
Dian Fathita Dwi Lestari ◽  
Agus Dwi Ananto
Keyword(s):  
Molecular Docking ◽  
Molecular Study ◽  
Synergy Effect ◽  
Structural Protein ◽  
Antiviral Compound ◽  
Docking Score ◽  
Antiviral Compounds ◽  
Natural Ligands ◽  
Docking Approach ◽  
Rapid Transmission

Rapid transmission of COVID-19 disease and the fatal effects of the disease lead researchers to use various way to find potential anti-COVID-19 compounds, including using modern approaches. Molecular docking is one of the methods that can be used to analyse antiviral compounds and its molecular target from Indonesian herbs that are believed to have properties as anti-COVID-19. This study aims to analyse antiviral compounds from 5 herbs that have the potential as inhibitors of PLpro and 3CLpro, which both are a non-structural protein in SARS-CoV-2 by molecular docking approach using PLANTS. Remdesivir triphosphate, the active metabolite of remdesivir, was used as the comparison compound in studies. The results showed docking scores obtained from interactions between natural ligands, remdesivir trifospat, curcumin, demetoksikurkumin, bisdemetoksikurkumin, luteolin, apigenin, kuersetin, kaempferol, formononrtin-7-O-glucoronide, androgafolide, and neoandrogafolide with PLpro are as follows -111,441, -103,827, -103,609, -102,363, -100,27,-79,6655, -78.6901, -80.9337, -79.4686, -82.1124, -79.1789, and -97.2452.Combination between quercetin, neoandrographolide, bisdemethoxycurcumin, demetoxycurcumin, and curcumin showed a synergy effect by reduce its docking score. Meanwhile its interaction with the protein 3CLpro showed docking score for those compounds as follows 64.0074, -86.1811, -81.428, -87.1625, -78.2899, -73.4345,-70,3368, -71.5539, -68.4321, -72.0154, -75.9777 and -93.7746.Combination between andrographolide, neoandrographolide, bisdemethoxycurcumin, demetoxycurcumin and curcumin, also shows synegy effect in 3CLpro allow them to reduce the docking score.This study concludes that curcumin was known as the most potent compound that act as a PLpro inhibitor based on a docking score of -103,609, while in 3CLpro all the compound have a potential to inhibit 3CLpro with demethosxycurcumin and  neoandrogafolide as the most potent compound with a docking score -87,126 and -93.7746.

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