scholarly journals Natures Therapy for COVID-19: Targeting the Vital Non-Structural Proteins (NSP) from SARS-CoV-2 with Phytochemicals from Indian Medicinal Plants

2020 ◽  
Author(s):  
Pratap Kumar Parida ◽  
Dipak Paul ◽  
Debamitra Chakravorty
Keyword(s):  
Medicinal Plants ◽  
Health Sector ◽  
Principal Component ◽  
Binding Energies ◽  
Structural Proteins ◽  
P Value ◽  
Pathway Enrichment Analysis ◽  
Binding Modes ◽  
Chemical Structures ◽  
Indian Medicinal Plants

Containing COVID-19 is still a global challenge. It has affected the "normal" world by<br>targeting its economy and health sector. Research is more focused on finding a cure to this<br>disease and is less concerned about other life threatening diseases like cancer. Thus we need to<br>develop a medical solution at the earliest. In this context the present work aimed to understand<br>the efficacy of 22 rationally screened phytochemicals from Indian medicinal plants obtained<br>from our previous work, following drug-likeness properties, against 6 non-structural-proteins<br>(NSP) from SARS-CoV-2. 100 ns molecular dynamics simulations were performed and<br>relative binding free energies were computed by MM/PBSA. Further, principal component<br>analysis, dynamic cross correlation and hydrogen bond occupancy were analyzed to<br>characterize protein–ligand interactions. Biological pathway enrichment analysis was also<br>carried out to elucidate the therapeutic targets of the phytochemicals in comparison to SARS-<br>CoV-2. The potential binding modes and favourable molecular interaction profile of 9<br>phytochemicals, majorly from Withania sominifera with lowest free binding energies, against<br>the SARS-CoV-2 NSP targets were identified. It was understood that phytochemicals and<br>repurposed drugs with steroidal moieties in their chemical structures formed stable interactions<br>with the NSPs. Additionally, human target pathway analysis for SARS-CoV-2 and<br>phytochemicals showed that cytokine mediated pathway and phosphorylation pathways were<br>with the most significant p-value. To summarize this work, we suggest a global approach of<br>targeting multiple proteins of SARS-CoV-2 with phytochemicals as a natural alternative<br>therapy for COVID-19. We also suggest that these phytochemicals need to be tested<br>experimentally to confirm their efficacy.

scholarly journals Natures Therapy for COVID-19: Targeting the Vital Non-Structural Proteins (NSP) from SARS-CoV-2 with Phytochemicals from Indian Medicinal Plants

2020 ◽  
Author(s):  
Pratap Kumar Parida ◽  
Dipak Paul ◽  
Debamitra Chakravorty
Keyword(s):  
Medicinal Plants ◽  
Health Sector ◽  
Principal Component ◽  
Binding Energies ◽  
Structural Proteins ◽  
P Value ◽  
Pathway Enrichment Analysis ◽  
Binding Modes ◽  
Chemical Structures ◽  
Indian Medicinal Plants

Containing COVID-19 is still a global challenge. It has affected the "normal" world by<br>targeting its economy and health sector. Research is more focused on finding a cure to this<br>disease and is less concerned about other life threatening diseases like cancer. Thus we need to<br>develop a medical solution at the earliest. In this context the present work aimed to understand<br>the efficacy of 22 rationally screened phytochemicals from Indian medicinal plants obtained<br>from our previous work, following drug-likeness properties, against 6 non-structural-proteins<br>(NSP) from SARS-CoV-2. 100 ns molecular dynamics simulations were performed and<br>relative binding free energies were computed by MM/PBSA. Further, principal component<br>analysis, dynamic cross correlation and hydrogen bond occupancy were analyzed to<br>characterize protein–ligand interactions. Biological pathway enrichment analysis was also<br>carried out to elucidate the therapeutic targets of the phytochemicals in comparison to SARS-<br>CoV-2. The potential binding modes and favourable molecular interaction profile of 9<br>phytochemicals, majorly from Withania sominifera with lowest free binding energies, against<br>the SARS-CoV-2 NSP targets were identified. It was understood that phytochemicals and<br>repurposed drugs with steroidal moieties in their chemical structures formed stable interactions<br>with the NSPs. Additionally, human target pathway analysis for SARS-CoV-2 and<br>phytochemicals showed that cytokine mediated pathway and phosphorylation pathways were<br>with the most significant p-value. To summarize this work, we suggest a global approach of<br>targeting multiple proteins of SARS-CoV-2 with phytochemicals as a natural alternative<br>therapy for COVID-19. We also suggest that these phytochemicals need to be tested<br>experimentally to confirm their efficacy.

scholarly journals Natures Therapy for COVID-19: Targeting the Vital Non-Structural Proteins (NSP) from SARS-CoV-2 with Phytochemicals from Indian Medicinal Plants

2020 ◽  
Author(s):  
Pratap Kumar Parida ◽  
Dipak Paul ◽  
Debamitra Chakravorty
Keyword(s):  
Medicinal Plants ◽  
Health Sector ◽  
Principal Component ◽  
Binding Energies ◽  
Structural Proteins ◽  
P Value ◽  
Pathway Enrichment Analysis ◽  
Binding Modes ◽  
Chemical Structures ◽  
Indian Medicinal Plants

Containing COVID-19 is still a global challenge. It has affected the "normal" world by<br>targeting its economy and health sector. Research is more focused on finding a cure to this<br>disease and is less concerned about other life threatening diseases like cancer. Thus we need to<br>develop a medical solution at the earliest. In this context the present work aimed to understand<br>the efficacy of 22 rationally screened phytochemicals from Indian medicinal plants obtained<br>from our previous work, following drug-likeness properties, against 6 non-structural-proteins<br>(NSP) from SARS-CoV-2. 100 ns molecular dynamics simulations were performed and<br>relative binding free energies were computed by MM/PBSA. Further, principal component<br>analysis, dynamic cross correlation and hydrogen bond occupancy were analyzed to<br>characterize protein–ligand interactions. Biological pathway enrichment analysis was also<br>carried out to elucidate the therapeutic targets of the phytochemicals in comparison to SARS-<br>CoV-2. The potential binding modes and favourable molecular interaction profile of 9<br>phytochemicals, majorly from Withania sominifera with lowest free binding energies, against<br>the SARS-CoV-2 NSP targets were identified. It was understood that phytochemicals and<br>repurposed drugs with steroidal moieties in their chemical structures formed stable interactions<br>with the NSPs. Additionally, human target pathway analysis for SARS-CoV-2 and<br>phytochemicals showed that cytokine mediated pathway and phosphorylation pathways were<br>with the most significant p-value. To summarize this work, we suggest a global approach of<br>targeting multiple proteins of SARS-CoV-2 with phytochemicals as a natural alternative<br>therapy for COVID-19. We also suggest that these phytochemicals need to be tested<br>experimentally to confirm their efficacy.

scholarly journals Tissue-based metabolomics profiling reveals metabolic signatures and major metabolic pathways of gastric cancer

2021 ◽  
Author(s):  
Yaqin Wang ◽  
Wenchao Chen ◽  
Kun Li ◽  
Gang Wu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Predictive Ability ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Pentose Phosphate ◽  
P Value ◽  
Pathway Enrichment Analysis ◽  
Dodecanoic Acid ◽  
Orthogonal Projections ◽  
Latent Structures

Abstract Purpose This study was aimed to screen differential metabolites between gastric cancer (GC) and paracancerous (PC) tissues and find new biomarkers of GC. Methods GC (n = 28) and matched PC (n = 28) tissues were collected and LC-MS/MS analyses were performed to detect metabolites of GC and PC tissues in positive and negative models. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminate analysis (OPLS-DA) were conducted to describe distribution of origin data and general separation and estimate the robustness and the predictive ability of our mode. Differential metabolites were screened based on criterion of variables with p value < 0.05 and VIP (variable importance in the projection) > 1.0. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to search for metabolite pathways and MetaboAnalyst was used for pathway enrichment analysis. Results Several metabolites were significantly changed in GC group compared with PC group. Thirteen metabolites with high VIP were chose and among which 1-methylnicotinamide, dodecanoic acid and sphinganine possessed high AUC values (AUC > 0.8) indicating an excellent discriminatory ability on GC. Pathways such as pentose phosphate pathway and histidine metabolism were focused based on differential metabolites demonstrating their effects on progress of GC. Conclusions In conclusion, we investigated the tissue-based metabolomics profile of GC and several differential metabolites and signaling pathways were focused. Further study is needed to verify those results.

scholarly journals In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3822 ◽  
Author(s):  
R.P. Vivek-Ananth ◽  
Abhijit Rana ◽  
Nithin Rajan ◽  
Himansu S. Biswal ◽  
Areejit Samal
Keyword(s):  
Medicinal Plants ◽  
Natural Product ◽  
Cathepsin L ◽  
Md Simulations ◽  
Binding Energies ◽  
In Vivo Testing ◽  
Approved Drugs ◽  
Indian Medicinal Plants

Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection. Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. Further, the ligand binding site residues and non-covalent interactions between protein and ligand were used as an additional filter to identify phytochemical inhibitors that either bind to or form interactions with residues important for the specificity of the target proteases. This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. Interestingly, several herbal sources of identified phytochemical inhibitors have antiviral or anti-inflammatory use in traditional medicine. Further in vitro and in vivo testing is needed before clinical trials of the promising phytochemical inhibitors identified here.

scholarly journals Nature to Nurture- Identifying Phytochemicals from Indian Medicinal Plants as Prophylactic Medicine by Rational Screening to Be Potent Against Multiple Drug Targets of SARS-CoV-2

2020 ◽  
Author(s):  
Pratap Kumar Parida ◽  
Dipak Paul ◽  
Debamitra Chakravorty
Keyword(s):  
Medicinal Plants ◽  
Drug Targets ◽  
Alternative Therapy ◽  
Health Sector ◽  
Multiple Drug ◽  
Natural Immunity ◽  
Protein Targets ◽  
Long Time ◽  
Potent Drug ◽  
Indian Medicinal Plants

The COVID-19 pandemic resulted in millions of people being quarantined, impacting the world economy and health sector. There is no existing proven treatment for this disease. It may takea long time until a good candidate vaccine or a potent drug is made available in the market. Therefore, there is a need to search for alternative therapy. In the context, this work explored natural compounds from Indian medicinal plants to develop a prophylactic treatment regimen that will be instrumentalin controlling the spread of the deadly virus. In this work 1916 phytochemicals from 55 Indian medicinal plants, reported to possess anti-viral properties, were subjected to virtual screening on 8 structural and non-structural SARS-CoV-2 protein targets. Docking interactions, ADME and toxicity profiles of the 66 screened phytochemicals were correlated with 21 repurposed drugs that have been most cited in literature to be effective against SARS-CoV-2. Steroidal lactones from Withaniasomnifera and triterpenoids from Azadirachtaindica- with docking score ranging from -13 kcal/mol upto -6 kcal/mol were identified to occupy the top scoring virtually screened phytochemicals against the various targets of SARS-CoV-2. Importantly this work proposes that a concoction of these phytochemicals can act as prophylactic anti-viral medicine to control the spread of SARS-CoV-2 and also enhance natural immunity as the first line of defence towards such a deadly virus.

scholarly journals Molecular Docking and Drug-Likeness for the Identification of Inhibitory Action of Acetogenins from Annona muricata as Potential Anticancer against Hypoxia Inducible Factor 1 Alpha

2018 ◽  
Vol 11 (3) ◽  
pp. 1301-1307
Author(s):  
Supri I. Handayani ◽  
Rahmiati Rahmiati ◽  
Lisnawati Rahmadi ◽  
Rosmalena Rosmalena ◽  
Vivitri D. Prasasty
Keyword(s):  
Molecular Docking ◽  
Hypoxia Inducible Factor ◽  
Binding Energies ◽  
Binding Modes ◽  
Annona Muricata ◽  
Chemical Structures ◽  
Hypoxia Inducible Factor 1 ◽  
Human Cancers

Hypoxia inducible factor 1 alpha (HIF-1α) regulates cell growth and differentiation which is implicated in human cancers. HIF-1α activates its cascade carcinogenesis mechanism in cancer cells. It is well-understood that signaling is initiated by HIF-1α receptor. Overexpression of HIF-1α is associated with several different human cancers, including breast cancer, lung cancer and colon cancer. Thus, HIF-1α becomes potential target of therapeutic approach in developing HIF-1α inhibitors. The aim of this research is to investigate potential inhibitors which are known as Acetogenins (AGEs) isolated from Annona muricata against HIF-1α. In order to achieve this goal, chemical structures of all compounds were retrieved from PubChem database. Molecular docking was performed by AutoDock Vina program and the resulting binding modes were analyzed with AutoDock Tools program. Among all the compounds, murihexocin A showed the best binding modes compared to other two inhibitors based on the lowest binding energies (LBE = -7.9 kcal/mol) as high as gefitinib. This was indicating that murihexocin A has favorable interaction with the essential amino acid residues at catalytic site of HIF-1α. Drug-likeness calculation of AGEs were also performed. These in silico results could be beneficial as a compound model for further studies in-vitro and in-vivo.

scholarly journals Nature to Nurture- Identifying Phytochemicals from Indian Medicinal Plants as Prophylactic Medicine by Rational Screening to Be Potent Against Multiple Drug Targets of SARS-CoV-2

2020 ◽  
Author(s):  
Pratap Kumar Parida ◽  
Dipak Paul ◽  
Debamitra Chakravorty
Keyword(s):  
Medicinal Plants ◽  
Drug Targets ◽  
Alternative Therapy ◽  
Health Sector ◽  
Multiple Drug ◽  
Natural Immunity ◽  
Protein Targets ◽  
Long Time ◽  
Potent Drug ◽  
Indian Medicinal Plants

The COVID-19 pandemic resulted in millions of people being quarantined, impacting the world economy and health sector. There is no existing proven treatment for this disease. It may takea long time until a good candidate vaccine or a potent drug is made available in the market. Therefore, there is a need to search for alternative therapy. In the context, this work explored natural compounds from Indian medicinal plants to develop a prophylactic treatment regimen that will be instrumentalin controlling the spread of the deadly virus. In this work 1916 phytochemicals from 55 Indian medicinal plants, reported to possess anti-viral properties, were subjected to virtual screening on 8 structural and non-structural SARS-CoV-2 protein targets. Docking interactions, ADME and toxicity profiles of the 66 screened phytochemicals were correlated with 21 repurposed drugs that have been most cited in literature to be effective against SARS-CoV-2. Steroidal lactones from Withaniasomnifera and triterpenoids from Azadirachtaindica- with docking score ranging from -13 kcal/mol upto -6 kcal/mol were identified to occupy the top scoring virtually screened phytochemicals against the various targets of SARS-CoV-2. Importantly this work proposes that a concoction of these phytochemicals can act as prophylactic anti-viral medicine to control the spread of SARS-CoV-2 and also enhance natural immunity as the first line of defence towards such a deadly virus.

On the Adsorption of Aspartate Derivatives to Calcite Surfaces in Aqueous Environment

2020 ◽  
Author(s):  
Robert Stepic ◽  
Lara Jurković ◽  
Ksenia Klementyeva ◽  
Marko Ukrainczyk ◽  
Matija Gredičak ◽  
...  
Keyword(s):  
Active Sites ◽  
Realistic Model ◽  
Binding Energies ◽  
Inhibition Mechanism ◽  
Aqueous Environment ◽  
Binding Modes ◽  
Carboxylate Groups ◽  
Dissolved Ions ◽  
Living Organisms ◽  
Dynamics Simulations

In many living organisms, biomolecules interact favorably with various surfaces of calcium carbonate. In this work, we have considered the interactions of aspartate (Asp) derivatives, as models of complex biomolecules, with calcite. Using kinetic growth experiments, we have investigated the inhibition of calcite growth by Asp, Asp2 and Asp3.This entailed the determination of a step-pinning growth regime as well as the evaluation of the adsorption constants and binding free energies for the three species to calcite crystals. These latter values are compared to free energy profiles obtained from fully atomistic molecular dynamics simulations. When using a flat (104) calcite surface in the models, the measured trend of binding energies is poorly reproduced. However, a more realistic model comprised of a surface with an island containing edges and corners, yields binding energies that compare very well with experiments. Surprisingly, we find that most binding modes involve the positively charged, ammonium group. Moreover, while attachment of the negatively charged carboxylate groups is also frequently observed, it is always balanced by the aqueous solvation of an equal or greater number of carboxylates. These effects are observed on all calcite features including edges and corners, the latter being associated with dominant affinities to Asp derivatives. As these features are also precisely the active sites for crystal growth, the experimental and theoretical results point strongly to a growth inhibition mechanism whereby these sites become blocked, preventing further attachment of dissolved ions and halting further growth.

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