Molecular Docking and ADMET Prediction of Natural Compounds towards SARS Spike Glycoprotein-Human Angiotensin-Converting Enzyme 2 and SARS-CoV-2 Main Protease
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ABSTRACT:
SUBMITTER: Oso B
PROVIDER: S-EPMC8605841 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent pandemic situation of COVID-19 is caused due to SARS-CoV2 and almost all the countries of the world have been affected by this highly contagious virus. Main protease (Mpro) of this virus is a highly attractive drug target among various other enzymes due to its ability to process poly-protein that is the translated product of the SARS-CoV2 RNA. The present study demonstrates molecular docking study of Glycyrrhiza glabra (Gg) active compounds such as Glycyrrhizic acid (GA), Liquiritigenin (L) and Glabridin (G) against the Mpro. Docking studies shows that these active compounds bind strongly with some of the amino acid residues in the active site of Mpro and inhibits the enzyme strongly. GA, L, and G are proposed to be strong inhibitors of the enzyme and the amino acids: His41, Gly143, Gln189, Glu 166, Cys 145, Thr25, Asn142, Met49, Cys44, Thr45 and pro168 present in the active site of Mpro were shown to make non-covalent interaction with these compounds. In silico ADMET properties prediction also shows that Gg active compounds had good solubility, absorption, permeation, non-toxic, and non- carcinogenic characteristics. Our finding concludes that all of the three active compounds of Gg have the potential to be strong inhibitors for Mpro of SARS-CoV2 but glycyrrhizic acid has a high binding affinity and a good ADMET properties than the other two.
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Project description:Since there is no general agreement on drug treatment of SARS-CoV-2, the search for a new drug capable of treating COVID-19 is of utmost priority. This study aims to dereplicate the chemical compounds of the methanol extract of Salvia officinalis and Artemisia dracunculus, and assay the inhibitory effect of these compounds as well as the previously dereplicated components of Zingiber officinale against SARS-CoV-2 in an in-silico study. A molecular networking (MN) technique was applied to find the chemical constituents of the extracts. Docking analysis was also used to find the binding affinity of dereplicated components from S. officinalis, A. dracunculus, and Z. officinale to COV-2-SP and Mpro. 57 compounds were dereplicated from the MeOH extracts of S. officinalis and A. dracunculus which include the class of polyphenols, flavonoids, coumarins, phenylpropanoids, anthocyanins, and dihydrochalcones. Molecular docking analysis indicated a high affinity of about 27 compounds from three mentioned plants against studied targets. kaempferol 3-O-rutinoside, neodiosmin, and querciturone with docking score values of -10.575, -10.208, and - 9.904 Kcal/mol and ki values of 0.016606, 0.030921, and 0.051749, respectively were found to have the highest affinities against COV-2-SP. 2-phenylethyl beta-primeveroside, curcumin PE, and kaempferol 3-O-rutinoside also indicated the highest affinity against Mpro with docking scores of -10.34, -10.126 and - 9.705 and ki values of 0.024726, 0.035529, and 0.072494, respectively. MN can be successfully used for the dereplication of metabolites from plant extracts. In addition, the in-silico binding energies introduced several inhibitors from Z. officinale, S. officinalis, and A. dracunculus for the treatment of SARS-CoV-2 disease.Supplementary informationThe online version contains supplementary material available at 10.1007/s11756-021-00881-z.
| S-EPMC8456686 | biostudies-literature
Project description:The coronavirus disease-2019 caused by a novel SARS CoV-2 virus has emerged as a global threat. Still, no drugs are available for its treatment. The main protease is the most conserved structure responsible for the posttranslational processing of non-structural polyproteins of this virus. Therefore, it can be the potential target for drug discovery against SARS CoV-2. Twenty-one thousand two hundred and seven chemical compounds used for sequential virtual screening studies including coronavirus screening compounds (Life Chemical database) and antiviral compounds (Asinex database). The Schrodinger suite 2019 employed for high throughput screening, molecular docking and MM-GBSA through the Glide module. Subsequently, 23 compounds were selected in the phase first selection criteria for re-docking with AutoDock and iDock followed by ADMET prediction. The drug-likeness predicted through Lipinski's rule of five, Veber's rule and Muegge's rule. Finally, three ligands were selected for molecular dynamics simulation studies over 150 ns against the main protease of the SARS CoV-2. They showed promising docking scores on Glide, iDock and AutoDock Vina algorithms (ligand F2679-0163: -10.75, -10.29 and -9.2; ligand F6355-0442: -9.38, -8.61 and -7.6; ligand 8250: -9.795, -7.94 and -7.5), respectively. The RMSD parameter remained stable at 2.5 Å for all the three ligands for 150 ns. The high RMSF fluctuations, RoG of around 22 Å and the binding free energy were favorable in each case. The hydrogen bond interactions of 8250, F6355-0442 and F2679-0163 were six, five and three, respectively. These compounds can be further explored for in vitro experimental validation against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.
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Project description:Nowadays, considering the spread of the coronavirus as a global threat, scientific research on this virus through simulation has been increasing. In this study, effect of Cu nanocluster on prevention and control of disease transmission was examined using molecular docking and molecular dynamics simulation studies on the SARS-CoV-2 main protease and spike glycoprotein. The cytotoxicity of different shapes of copper NPs and resonance changes of their surface plasmons on inactivation of the coronavirus was examined in order to control replication of coronavirus through copper NPs, active site of protease and spike glycoprotein. The simulations results showed that interactions of SARS-CoV-2 main protease and spike glycoprotein target and cylindrical and conical copper NPs ligands were more efficient than spherical copper NPs.
| S-EPMC8719269 | biostudies-literature
Project description:In this study, chemical investigation of methanol extract of the air-dried fruits of Luffa cylindrica led to the identification of a new δ-valerolactone (1), along with sixteen known compounds (2-17). Their chemical structures including the absolute configuration were elucidated by extensive spectroscopic analysis and electronic circular dichroism analysis, as well as by comparison with those reported in the literature. For the first time in literature, we have examined the binding potential of the isolated compounds to highly conserved protein, Mpro of SARS-CoV-2 using the molecular docking technique. We found that the isolated saponins (14-17) bind to the substrate-binding pocket of SARS-CoV-2 Mpro with docking energy scores of -7.13, -7.29, -7.47, and -7.54 kcal.mol-1, respectively, along with binding abilities equivalent to an already claimed N3 protease inhibitor (-7.51 kcal.mol-1).
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Project description:A recent experimental study found that the binding affinity between the cellular receptor human angiotensin-converting enzyme 2 (ACE2) and receptor-binding domain (RBD) in the spike (S) protein of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is more than tenfold higher than that of the original severe acute respiratory syndrome coronavirus (SARS-CoV). However, main chain structures of the SARS-CoV-2 RBD are almost the same with that of the SARS-CoV RBD. Understanding the physical mechanism responsible for the outstanding affinity between the SARS-CoV-2 S and ACE2 is an "urgent challenge" for developing blockers, vaccines, and therapeutic antibodies against the coronavirus disease 2019 (COVID-19) pandemic. Taking into account the mechanisms of hydrophobic interaction, hydration shell, surface tension, and the shielding effect of water molecules, this study reveals a hydrophobic-interaction-based mechanism by means of which SARS-CoV-2 S and ACE2 bind together in an aqueous environment. The hydrophobic interaction between the SARS-CoV-2 S and ACE2 protein is found to be significantly greater than that between SARS-CoV S and ACE2. At the docking site, the hydrophobic portions of the hydrophilic side chains of SARS-CoV-2 S are found to be involved in the hydrophobic interaction between SARS-CoV-2 S and ACE2.
| S-EPMC7646041 | biostudies-literature
Project description:An outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been recognized as a global health concern. Since, no specific antiviral drug is proven effective for treatment against COVID-19, identification of new therapeutics is an urgent need. In this study, flavonoid compounds were analyzed for its inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. Virtual docking was performed for screening of flavonoid compounds retrieved from PubChem against the main protease of SARS-CoV-2 using COVID-19 docking server. The cut off of dock score was set to >-9 kcal/mol and screened compounds were individually docked against main protease, RNA-dependent RNA polymerase, and spike proteins using AutoDock 4.1 software. Finally, lead flavonoid compounds were subjected to ADMET analysis. A total of 458 flavonoid compounds were virtually screened against main protease target and 36 compounds were selected based on the interaction energy value >-9 kcal/mol. Furthermore, these compounds were individually docked against protein targets and top 10 lead compounds were identified. Among the lead compounds, agathisflavone showed highest binding energy value of -8.4 kcal/mol against main protease, Albireodelphin showed highest dock score of -9.8 kcal/mol and -11.2 kcal/mol against RdRp, and spike proteins, respectively. Based on the high dock score and ADMET properties, top 5 lead molecules such as Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate were identified as potent inhibitors against main protease, RdRp, and spike protein targets of SARS-CoV-2. These all compounds are having non-carcinogenic and non-mutagenic properties. This study finding suggests that the screened compounds include Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate could be the potent inhibitors of SARS-CoV-2 targets.
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Project description:The main protease (Mpro) of SARS-CoV-2 is an appealing target for the development of antiviral compounds, due to its critical role in the viral life cycle and its high conservation among different coronaviruses and the continuously emerging mutants of SARS-CoV-2. Ferulic acid (FA) is a phytochemical with several health benefits that is abundant in plant biomass and has been used as a basis for the enzymatic or chemical synthesis of derivatives with improved properties, including antiviral activity against a range of viruses. This study tested 54 reported FA derivatives for their inhibitory potential against Mpro by in silico simulations. Molecular docking was performed using Autodock Vina, resulting in comparable or better binding affinities for 14 compounds compared to the known inhibitors N3 and GC376. ADMET analysis showed limited bioavailability but significantly improved the solubility for the enzymatically synthesized hits while better bioavailability and druglikeness properties but higher toxicity were observed for the chemically synthesized ones. MD simulations confirmed the stability of the complexes of the most promising compounds with Mpro, highlighting FA rutinoside and compound e27 as the best candidates from each derivative category.
| S-EPMC9329733 | biostudies-literature
Project description:In the absence of efficient anti-viral medications, the coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), has spawned a worldwide catastrophe and global emergency. Amidst several anti-viral targets of COVID-19, spike glycoprotein has been recognized as an essential target for the viral entry into the host cell. In the search of effective SARS CoV-2 inhibitors acting against spike glycoprotein, the virtual screening of 175,851 ligands from the 2020.1 Asinex BioDesign library has been performed using in silico tools like SiteMap analysis, pharmacophore-based screening, molecular docking using different levels of precision, such as high throughput virtual screening, standard precision and extra precision, followed by absorption, distribution, metabolism, excretion and toxicity analysis, and molecular dynamics (MD) simulation. Following a molecular docking study, seventeen molecules (with a docking score of less than - 6.0) were identified having the substantial interactions with the catalytic amino acid and nucleic acid residues of spike glycoprotein at the binding site. In investigations using MD simulations for 10 ns, the hit molecules (1 and 2) showed adequate compactness and uniqueness, as well as satisfactory stability. These computational research findings have offered a key starting point in the field of design and development of novel SARS CoV-2 entry inhibitors with appropriate drug likeliness.
| S-EPMC8821869 | biostudies-literature
Project description:Cinnamon has been utilized to remedy a lot of afflictions of humans. Literary works illustrate that it possesses numerous biological activities. Our research study is intended to recognize the phyto-derived antiviral substances from Cinnamon against COVID-19 main protease enzyme and to understand the in silico molecular basis of its activity. In the present study, 48 isolates compounds from Cinnamon retrieved from the PubMed database, are subjected to docking analysis. Docking study was performed using Autodock vina and PyRx software. Afterwards, admetSAR, as well as DruLiTo servers, were used to investigate drug-likeness prophecy. Our study shows that the nine phytochemicals of Cinnamon are very likely against the main protease enzyme of COVID-19. Further MD simulations could identify Tenufolin (TEN) and Pavetannin C1 (PAV) as hit compounds. Utilizing contemporary strategies, these phyto-compounds from a natural origin might establish a reliable medication or support lead identification. Identified hit compounds can be further taken for in vitro and in vivo studies to examine their effectiveness versus COVID-19.
| S-EPMC7332870 | biostudies-literature