scholarly journals Exploring Phytochemicals of Traditional Medicinal Plants Exhibiting Inhibitory Activity Against Main Protease, Spike Glycoprotein, RNA-dependent RNA Polymerase and Non-Structural Proteins of SARS-CoV-2 Through Virtual Screening

2021 ◽  
Vol 12 ◽  
Author(s):  
Saranya Nallusamy ◽  
Jayakanthan Mannu ◽  
Caroline Ravikumar ◽  
Kandavelmani Angamuthu ◽  
Bharathi Nathan ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Inhibitory Activity ◽  
Mangifera Indica ◽  
Herbal Medicines ◽  
Genomic Analysis ◽  
Zingiber Officinale ◽  
Binding Energies ◽  
New Drugs ◽  
Cissus Quadrangularis ◽  
Scientific Attention

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) being a causative agent for global pandemic disease nCOVID’19, has acquired much scientific attention for the development of effective vaccines and drugs. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune-boosting activity against SARS-CoV-2. In this study, efforts were made to examine the potential of 605 phytochemicals from 37 plant species (of which 14 plants were endemic to India) and 139 antiviral molecules (Pubchem and Drug bank) in inhibiting SARS-CoV-2 multiple protein targets through a virtual screening approach. Results of our experiments revealed that SARS-CoV-2 MPro shared significant disimilarities against SARS-CoV MPro and MERS-CoV MPro indicating the need for discovering novel drugs. This study has screened the phytochemical cyanin (Zingiber officinale) which may exhibit broad-spectrum inhibitory activity against main proteases of SARS-CoV-2, SARS-CoV and MERS-CoV with binding energies of (−) 8.3 kcal/mol (−) 8.2 kcal/mol and (−) 7.7 kcal/mol respectively. Amentoflavone, agathisflavone, catechin-7-o-gallate and chlorogenin were shown to exhibit multi-target inhibitory activity. Further, Mangifera indica, Anacardium occidentale, Vitex negundo, Solanum nigrum, Pedalium murex, Terminalia chebula, Azadirachta indica, Cissus quadrangularis, Clerodendrum serratum and Ocimum basilicumaree reported as potential sources of phytochemicals for combating nCOVID’19. More interestingly, this study has highlighted the anti-viral properties of the traditional herbal formulation “Kabasura kudineer” recommended by AYUSH, a unit of Government of India. Short listed phytochemicals could be used as leads for future drug design and development. Genomic analysis of identified herbal plants will help in unraveling molecular complexity of therapeutic and anti-viral properties which proffer lot of chance in the pharmaceutical field for researchers to scout new drugs in drug discovery.

scholarly journals Shortlisting Phytochemicals Exhibiting Inhibitory Activity against Major Proteins of SARS-CoV-2 through Virtual Screening

2020 ◽  
Author(s):  
Saranya Nallusamy ◽  
Jayakanthan Mannu ◽  
Caroline Ravikumar ◽  
Kandavelmani Angamuthu ◽  
Bharathi Nathan ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Inhibitory Activity ◽  
Mangifera Indica ◽  
Herbal Medicines ◽  
Genomic Analysis ◽  
Zingiber Officinale ◽  
Major Protein ◽  
Synthetic Drugs ◽  
Cissus Quadrangularis ◽  
Control And Management

Abstract Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) declared as a pandemic by WHO that has affected more than 40 lakh peoples and caused death of more than 2 lakh individuals across the globe. Limited availability of genomic information of SARS-CoV-2 and non-availability of vaccines and effective drugs are major problems responsible for the ineffective control and management of this pandemic. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune boosting activity against SARS-CoV-2.In this study, efforts were made to examine the potential of 721 phytochemicals of 37 plant species in inhibiting major protein targets namely, spike glycoprotein, main protease (MPro), NSP3, NSP9, NSP15, NSP10-NSP16 and RNA dependent RNA polymerase of SARS-CoV-2 through virtual screening approach. Results of our experiments revealed that SARS-CoV-2 MPro shared significant dissimilarities against SARS-CoVMPro and MERS-CoVMPro indicating the need for discovering novel drugs. This study has identified the phytochemical cyanin (Zingiber officinale) exhibiting broad spectrum inhibitory activity against main proteases of all the three Coronaviruses. Amentoflavone, agathisflavone, catechin-7-o-gallate and chlorogeninwere shown to exhibit multi target inhibitory activity. This study has identified Mangifera indica, Anacardium occidentale, Vitex negundo, Solanum nigrum, Pedalium murex, Terminalia chebula, Azadirachta indica, Cissus quadrangularis, Clerodendrum serratum and Ocimum basilicum as potential sources of phytochemicals combating nCOVID-19. More interestingly, this study has generated evidences for the anti-viral properties of the traditional herbal formulation “Kabasura kudineer” recommended by AYUSH, a unit of Government of India. Testing of short listed phytochemicals through clinical trials will help in developing effective formulation for management of this pandemic disease. Genomic analysis of identified herbal plants will help in unravelling molecular complexity of therapeutic and anti-viral properties and will pave way for designing synthetic drugs.

scholarly journals EVALUATION OF XANTHINE OXIDASE INHIBITORY ACTIVITY BY FLAVONOIDS FROM PONGAMIA PINNATA LINN

2017 ◽  
Vol 10 (3) ◽  
pp. 360 ◽  
Author(s):  
Vanishree Bambrana ◽  
Dayanand Cd ◽  
Sheela Sr
Keyword(s):  
Xanthine Oxidase ◽  
Plant Extracts ◽  
Inhibitory Activity ◽  
Mangifera Indica ◽  
Zingiber Officinale ◽  
Pongamia Pinnata ◽  
Morinda Citrifolia ◽  
Dried Fruit ◽  
Fruit Powder ◽  
Inhibitory Potential

ABSTRACTObjective: Flavonoids from the crude seeds extract of Pongamia pinnata L., dried fruit powder of Morinda citrifolia L., bark of Mangifera indica L., andrhizome of Zingiber officinale Rosc. were screened for xanthine oxidase (XO) inhibition at different concentration. The inhibitory potential of quercetinand allopurinol were used for the determination of 50% inhibitory concentration (IC50) and Ki values.Methods: Isolation of flavonoids from the plant extracts was processed by column chromatography and tested for XO inhibitory activity in the rangeof 6-800 μg/ml.Results: The results demonstrated that optimized flavonoids extract of P. pinnata L. exhibited promising XO inhibition. P. pinnata L., M. indica L., andZ. officinale Rosc. had IC50 in the concentration of 8.74 mM, 1.09 mM, 5.4 mM and Ki 0.35 mM, 1.73 mM, 2.7 mM, respectively.Conclusion: The study showed that plant species under investigation exhibited XO inhibition by optimized flavonoid extract. P. pinnata L. indicatedpromising XO inhibition compared to other plant extracts. Flavonoids can be used as a potent inhibitor of XO an alternative to allopurinol.Keywords: Xanthine oxidase, Quercetin, Allopurinol, Pongamia pinnata, Oxidative stress.

Virtual Screening, Molecular Dynamics and ADME-Tox Tools for Finding Potential Inhibitors of Phosphoglycerate Mutase 1 from Plasmodium falciparum

2018 ◽  
Vol 18 (18) ◽  
pp. 1610-1617 ◽  
Author(s):  
Lluvia Ríos-Soto ◽  
Claudia Avitia-Domínguez ◽  
Erick Sierra-Campos ◽  
Mónica Valdez-Solana ◽  
Jorge Cisneros-Martínez ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Structural Changes ◽  
Treatment Resistance ◽  
Binding Energies ◽  
New Drugs ◽  
Phosphoglycerate Mutase ◽  
Chemical Library ◽  
Starting Point ◽  
Potential Inhibitors ◽  
Molecular Dynamic Analysis

Background: Nowadays, malaria is still one of the most important and lethal diseases worldwide, causing 445,000 deaths in a year. Due to the actual treatment resistance, there is an emergency to find new drugs. Objective: The aim of this work was to find potential inhibitors of phosphoglycerate mutase 1 from P. falciparum. Results: Through virtual screening of a chemical library of 15,123 small molecules, analyzed by two programs, four potential inhibitors of phosphoglycerate mutase 1 from P. falciparum were found: ZINC64219552, ZINC39095354, ZINC04593310, and ZINC04343691; their binding energies in SP mode were -7.3, -7.41, -7.4, and -7.18 kcal/mol respectively. Molecular dynamic analysis revealed that these molecules interact with residues important for enzyme catalysis and molecule ZINC04343691 provoked the highest structural changes. Physiochemical and toxicological profiles evaluation of these inhibitors with ADME-Tox method suggested that they can be considered as potential drugs. Furthermore, analysis of human PGAM-B suggested that these molecules could be selective for the parasitic enzyme. Conclusion: The compounds reported here are the first selective potential inhibitors of phosphoglycerate mutase 1 from P. falciparum, and can serve as a starting point in the search of a new chemotherapy against malaria.

scholarly journals Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of COVID-19 Main Protease: A Virtual Drug Repurposing Study

2020 ◽  
Author(s):  
Serdar Durdagi ◽  
Busecan Aksoydan ◽  
Berna Dogan ◽  
Kader Sahin ◽  
Aida Shahraki
Keyword(s):  
Virtual Screening ◽  
Clinical Investigation ◽  
Drug Repurposing ◽  
Md Simulations ◽  
Binding Energies ◽  
New Drugs ◽  
Docking Simulations ◽  
New Drug ◽  
Main Protease ◽  
Glide Docking

<div>There is an urgent need for a new drug against COVID-19. Since designing a new drug and testing its pharmacokinetics and pharmacodynamics properties may take years, here we used a physics-driven high throughput virtual screening drug re-purposing approach to identify new compounds against COVID-19. As the molecules considered in repurposing studies passed through several stages and have well-defined profiles, they would not require prolonged preclinical studies and hence, they would be excellent candidates in the cases of disease emergencies or outbreaks. While the spike protein is the key for the virus to enter the cell though the interaction with ACE2, enzymes such as main protease are crucial for the life cycle of the virus. This protein is one of the most attractive targets for the development of new drugs against</div><div>COVID-19 due to its pivotal role in the replication and transcription of the virus. We used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH Chemical Genomics Center (NCGC) Pharmaceutical Collection (NPC) database in our drug repurposing study. Both apo and holo forms of target protein COVID-19 main proteases were used in virtual screening. Target proteins were retrieved from protein data bank (PDB IDs, 6M03 and 6LU7). Standard Precision (SP) protocol of Glide docking program of Maestro was used in docking. Compounds were then ranked based on their docking scores that represents binding energies. Top-30 compounds from each docking simulations were considered initially in short (10-ns) molecular dynamics (MD) simulations and their average binding energies using collected 1000 trajectories throughout the MD simulations were calculated by Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method. Selected promising hit compounds based on average MM/GBSA scores were then used in long (100-ns) MD simulations. These numerical calculations showed that the following 6 compounds can be considered as COVID-19 Main Protease inhibitors: Lasinavir, Brecanavir, Telinavir, Rotigaptide, 1,3-Bis-(2-ethoxycarbonylchromon-5-yloxy)-2-(lysyloxy)propane and Pimelautide.</div>

Herbal Medicine: Clinical Perspective & Regulatory Status

2020 ◽  
Vol 23 ◽  
Author(s):  
Md Abul Barkat ◽  
Anjali Goyal ◽  
Harshita Abul Barkat ◽  
Mohammad Salauddin ◽  
Faheem Hyder Pottoo ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Herbal Medicines ◽  
New Drugs ◽  
Herbal Drugs ◽  
Clinical Perspective ◽  
Regulatory Status ◽  
Novel Drugs ◽  
History Of ◽  
Pros And Cons ◽  
Health Complications

Abstract:: Herbal medicines pays an important in treating the vaious diseases mainly due to the their potentially high therapeutic values and also due to the better acceptance of vaioruspatient under different health complications. The herbal medicine practice involves use of part of plant, entire plant or the selectctive isolated phytomedicineand the use and practices based on these has its pros and cons and has been greatly affected during the dawn. The search of new drugs during scientific era revives the interest in discovery of herbal drugs from different natural resources during 20th century. The present modern healthcare system invovlves utilization drugs and 50% of them are of ofnaural origin. Herbal drug disocovery found to be highly costly affair with low success rate and it hinders the further progress in utilizting the phytomedicine in treating the various deseases. But in recent years there is an increase in the search interest of herbal drugs mainly by the pharmaceutical industry and those invoves in the search of novel drugs from the herbs. Discovery of such new novel phytomedicines has to overcomes various challenges in indentification of active extracts and their toxicity, advereffects, herb drug interaction and importantly their regulatory requirments. The present review mainly focused on the history of herbal medicine, current clinical perspective, pharmaceutical, and regulatory challenges as well as its clinical presentation. Moreover, problems encountered in drug discovery from herbal resources and its possible solutions are delineated.

Virtual Screening Meets Deep Learning

2018 ◽  
Vol 15 (1) ◽  
pp. 6-28 ◽  
Author(s):  
Javier Pérez-Sianes ◽  
Horacio Pérez-Sánchez ◽  
Fernando Díaz
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Deep Learning ◽  
Virtual Screening ◽  
Great Increase ◽  
New Drugs ◽  
Learning Approach ◽  
Screening Strategies ◽  
Computer Aided ◽  
Recent Developments

Background: Automated compound testing is currently the de facto standard method for drug screening, but it has not brought the great increase in the number of new drugs that was expected. Computer- aided compounds search, known as Virtual Screening, has shown the benefits to this field as a complement or even alternative to the robotic drug discovery. There are different methods and approaches to address this problem and most of them are often included in one of the main screening strategies. Machine learning, however, has established itself as a virtual screening methodology in its own right and it may grow in popularity with the new trends on artificial intelligence. Objective: This paper will attempt to provide a comprehensive and structured review that collects the most important proposals made so far in this area of research. Particular attention is given to some recent developments carried out in the machine learning field: the deep learning approach, which is pointed out as a future key player in the virtual screening landscape.

scholarly journals Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gongming Li ◽  
Qingqing Guo ◽  
Chao Feng ◽  
Huan Chen ◽  
Wenjiao Zhao ◽  
...  
Keyword(s):  
Schistosoma Japonicum ◽  
Inhibitory Activity ◽  
Pyridine Ring ◽  
New Drugs ◽  
Wild Type ◽  
Drug Candidates ◽  
Structure Activity ◽  
Docking Method ◽  
Antigen Protein ◽  
Thioredoxin Glutathione Reductase

Abstract Background Schistosomiasis is a chronic parasitic disease that affects millions of people’s health worldwide. Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR). Methods In this work, one of the oxadiazole-2-oxides derivatives furoxan was used as the lead compound to exploit a series of novel furoxan derivatives for studying inhibitory activity against both recombinant Schistosoma japonicum TGR containing selenium (rSjTGR-Sec) and soluble worm antigen protein (SWAP) containing wild-type Schistosoma japonicum TGR (wtSjTGR), in order to develop a new leading compound for schistosomiasis. Thirty-nine novel derivatives were prepared to test their activity toward both enzymes. The docking method was used to detect the binding site between the active molecule and SjTGR. The structure–activity relationship (SAR) of these novel furoxan derivatives was preliminarily analyzed. Results It was found that several new derivatives, including compounds 6a–6d, 9ab, 9bd and 9be, demonstrated greater activity toward rSjTGR-Sec or SWAP containing wtSjTGR than did furoxan. Interestingly, all intermediates bearing hydroxy (6a–6d) showed excellent inhibitory activity against both enzymes. In particular, compound 6d with trifluoromethyl on a pyridine ring was found to have much higher inhibition toward both rSjTGR-Sec (half-maximal inhibitory concentration, IC50,7.5nM) and SWAP containing wtSjTGR (IC50 55.8nM) than furoxan. Additionally, the docking method identified the possible matching sites between 6d and Schistosoma japonicum TGR (SjTGR), which theoretically lends support to the inhibitory activity of 6d. Conclusion The data obtained herein showed that 6d with trifluoromethyl on a pyridine ring could be a valuable leading compound for further study.

scholarly journals The inhibitory activity of herbal medicines on the keys enzymes and steps related to carbohydrate and lipid digestion

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Weerachat Sompong ◽  
Nuttapat Muangngam ◽  
Artitaya Kongpatpharnich ◽  
Chadakarn Manacharoenlarp ◽  
Chanatkarn Amorworasin ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Herbal Medicines ◽  
Lipid Digestion

scholarly journals Novel Transforming Growth Factor-Beta Receptor 1 Antagonists through a Pharmacophore-Based Virtual Screening Approach

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2824 ◽  
Author(s):  
Junhao Jiang ◽  
Hui Zhou ◽  
Qihua Jiang ◽  
Lili Sun ◽  
Ping Deng
Keyword(s):  
Growth Factor ◽  
Virtual Screening ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Malignant Tumors ◽  
Pharmacophore Model ◽  
New Drugs ◽  
Beta Receptor ◽  
Potential Activity ◽  
Growth Factor Beta

As new drugs for the treatment of malignant tumors, transforming growth factor-beta receptor 1 (TGFβR1) antagonists have attracted wide attention. Based on the crystal structure of TGFβR1-BMS22 complex, the pharmacophore model A02 with two hydrogen bond acceptors (HBAs) and four hydrophobic (HYD) properties was constructed. From the common features of active ligands reported in the literature, pharmacophore model B10 was also generated, which has two aromatic ring centers (RAs) and two HYD properties. The two models have high sensitivity and specificity to the training set, and they are highly consistent in spatial structure. Combining the two pharmacophore models, two novel skeleton structures with potential activity were selected by virtual screening from the DruglikeDiverse, MiniMaybridge, and ZINC Drug-Like databases. Four compounds (YXY01–YXY04) with potential anti-TGFβR1 activity were designed based on the new skeleton structures. In combination with Lipinski’s rules; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and, toxicological properties predicted in the study, YXY01-03 with the novel skeleton, good drug-like properties, and potential activity were finally discovered and may have higher safety relative to BMS22, which may be valuable for further research.

scholarly journals Advances in the Treatment of Explicit Water Molecules in Docking and Binding Free Energy Calculations

2020 ◽  
Vol 26 (42) ◽  
pp. 7598-7622 ◽  
Author(s):  
Xiao Hu ◽  
Irene Maffucci ◽  
Alessandro Contini
Keyword(s):  
Drug Discovery ◽  
Binding Free Energy ◽  
Docking Studies ◽  
Free Energy Calculations ◽  
Binding Energies ◽  
New Drugs ◽  
Water Molecules ◽  
Open Questions ◽  
Dynamics Simulations ◽  
Computational Drug Discovery

Background: The inclusion of direct effects mediated by water during the ligandreceptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions. Objective: In this review, we will discuss some of the most recent methods that can be used in computational drug discovery and drug development when the effect of a single water, or of a small network of interacting waters, needs to be explicitly considered. Results: Here, we analyse the software to aid the selection, or to predict the position, of water molecules that are going to be explicitly considered in later docking studies. We also present software and protocols able to efficiently treat flexible water molecules during docking, including examples of applications. Finally, we discuss methods based on molecular dynamics simulations that can be used to integrate docking studies or to reliably and efficiently compute binding energies of ligands in presence of interfacial or bridging water molecules. Conclusions: Software applications aiding the design of new drugs that exploit water molecules, either as displaceable residues or as bridges to the receptor, are constantly being developed. Although further validation is needed, workflows that explicitly consider water will probably become a standard for computational drug discovery soon.

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