Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In silico approach of secondary metabolites from Brazilian herbal medicines to search for potential drugs against SARS-CoV-2.

ABSTRACT: The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti-SARS-CoV-2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS-CoV-2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti-COVID-19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID-19 treatment.

SUBMITTER: Amparo TR

PROVIDER: S-EPMC8250981 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

<i>In silico</i> identification of natural compounds against SARS-CoV-2 main protease from Chinese herbal medicines.

Project description:AimsTo determine natural compounds with inhibitory effects toward SARS-CoV-2 Mpro from Chinese herbal medicines.Materials & methods∼1200 natural compounds from 19 Chinese herbal medicines were collected. Computational methods including molecular docking, drug-likeness assessment, molecular dynamics simulation and molecular mechanics Poisson-Boltzmann surface area analysis were combined to obtain potent inhibitors against SARS-CoV-2 Mpro.ResultsTop 20 compounds mainly originated from Ranunculus ternatus and Picrasma quassioides exhibited low binding free energies which below -9.0 kcal/mol. Compounds Japonicone G and Picrasidine T were obtained with favorable drug-likeness. Moreover, the complex of Japonicone G and Mpro had prominent stability.ConclusionNatural compound Japonicone G is highly promising as a potent inhibitor against SARS-CoV-2 for further study.

| S-EPMC10357396 | biostudies-literature

In Silico Screening of the DrugBank Database to Search for Possible Drugs against SARS-CoV-2.

Project description:Coronavirus desease 2019 (COVID-19) is responsible for more than 1.80 M deaths worldwide. A Quantitative Structure-Activity Relationships (QSAR) model is developed based on experimental pIC50 values reported for a structurally diverse dataset. A robust model with only five descriptors is found, with values of R2 = 0.897, Q2LOO = 0.854, and Q2ext = 0.876 and complying with all the parameters established in the validation Tropsha's test. The analysis of the applicability domain (AD) reveals coverage of about 90% for the external test set. Docking and molecular dynamic analysis are performed on the three most relevant biological targets for SARS-CoV-2: main protease, papain-like protease, and RNA-dependent RNA polymerase. A screening of the DrugBank database is executed, predicting the pIC50 value of 6664 drugs, which are IN the AD of the model (coverage = 79%). Fifty-seven possible potent anti-COVID-19 candidates with pIC50 values > 6.6 are identified, and based on a pharmacophore modelling analysis, four compounds of this set can be suggested as potent candidates to be potential inhibitors of SARS-CoV-2. Finally, the biological activity of the compounds was related to the frontier molecular orbitals shapes.

| S-EPMC7923184 | biostudies-literature

Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection.

Project description:The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti-SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx were effective in a challenge study using hamsters as disease model.

| S-EPMC7865145 | biostudies-literature

In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis.

Project description:Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein-receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3'-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.

| S-EPMC7689506 | biostudies-literature

A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19).

Project description:The epidemic of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection has been listed as a public health emergency of international concern by the World Health Organization (WHO), and its harm degree is defined as a global "pandemic". At present, the efforts of various countries focus on the rapid diagnosis and isolation of patients, as well as to find a treatment that can combat the most serious impact of the disease. The number of reported COVID-19 virus infections is still increasing. Unfortunately, no drugs or vaccines have been approved for the treatment of human coronaviruses, but there is an urgent need for in-depth research on emerging human infectious coronaviruses. Clarification transmission routes and pathogenic mechanisms, and identification of potential drug treatment targets will promote the development of effective prevention and treatment measures. In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. This review summarizes the epidemiological characteristics, pathogenesis, virus structure and targeting strategies of COVID-19. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19.

| S-EPMC7237953 | biostudies-literature

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance.

Project description:The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure to obtain a therapeutic response. This narrative review focuses on clinical studies improving knowledge on the ability of selected herbal medicines to influence the pharmacokinetics of co-administered drugs. Moreover, in vitro studies are useful to anticipate potential herbal medicine-drug interactions. In particular, they help to elucidate the cellular target (metabolic or transporter protein) and the mechanism (induction or inhibition) by which a single constituent of the herbal medicine acts. The authors highlight the difficulties in predicting herbal-drug interactions from in vitro data where high concentrations of extracts or their constituents are used and pharmacokinetics are missed. Moreover, the difficulty to compare results from human studies where different kinds of herbal extracts are used is discussed. The herbal medicines discussed are among the best sellers and they are reported in the "Herbal Medicines for Human Use" section of the European Medicinal Agency (EMA).

| S-EPMC7400069 | biostudies-literature

The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals.

Project description:Recently, the emergence and spread of pathogenic bacterial resistance to many antibiotics (multidrug-resistant strains) have been increasing throughout the world. This phenomenon is of great concern and there is a need to find alternative chemotherapeutic agents to combat these antibiotic-resistant microorganisms. Higher plants may serve as a resource for new antimicrobials to replace or augment current therapeutic options. In this work, we have carried out a molecular docking study of a total of 561 antibacterial phytochemicals listed in the Dictionary of Natural Products, including 77 alkaloids (17 indole alkaloids, 27 isoquinoline alkaloids, 4 steroidal alkaloids, and 28 miscellaneous alkaloids), 99 terpenoids (5 monoterpenoids, 31 sesquiterpenoids, 52 diterpenoids, and 11 triterpenoids), 309 polyphenolics (87 flavonoids, 25 chalcones, 41 isoflavonoids, 5 neoflavonoids, 12 pterocarpans, 10 chromones, 7 condensed tannins, 11 coumarins, 30 stilbenoids, 2 lignans, 5 phenylpropanoids, 13 xanthones, 5 hydrolyzable tannins, and 56 miscellaneous phenolics), 30 quinones, and 46 miscellaneous phytochemicals, with six bacterial protein targets (peptide deformylase, DNA gyrase/topoisomerase IV, UDP-galactose mutase, protein tyrosine phosphatase, cytochrome P450 CYP121, and NAD?-dependent DNA ligase). In addition, 35 known inhibitors were docked with their respective targets for comparison purposes. Prenylated polyphenolics showed the best docking profiles, while terpenoids had the poorest. The most susceptible protein targets were peptide deformylases and NAD?-dependent DNA ligases.

| S-EPMC5039526 | biostudies-literature

Crystallographic molecular replacement using an in silico-generated search model of SARS-CoV-2 ORF8.

Project description:The majority of crystal structures are determined by the method of molecular replacement (MR). The range of application of MR is limited mainly by the need for an accurate search model. In most cases, pre-existing experimentally determined structures are used as search models. In favorable cases, ab initio predicted structures have yielded search models adequate for MR. The ORF8 protein of SARS-CoV-2 represents a challenging case for MR using an ab initio prediction because ORF8 has an all β-sheet fold and few orthologs. We previously determined experimentally the structure of ORF8 using the single anomalous dispersion (SAD) phasing method, having been unable to find an MR solution to the crystallographic phase problem. Following a report of an accurate prediction of the ORF8 structure, we assessed whether the predicted model would have succeeded as an MR search model. A phase problem solution was found, and the resulting structure was refined, yielding structural parameters equivalent to the original experimental solution.

| S-EPMC7980513 | biostudies-literature

Implication of in silico studies in the search for novel inhibitors against SARS-CoV-2.

Project description:Corona Virus Disease-19 (COVID-19) is a pandemic disease mainly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It had spread from Wuhan, China, in late 2019 and spread over 222 countries and territories all over the world. Earlier, at the very beginning of COVID-19 infection, there were no approved medicines or vaccines for combating this disease, which adversely affected a lot of individuals worldwide. Although frequent mutation leads to the generation of more deadly variants of SARS-CoV-2, researchers have developed several highly effective vaccines that were approved for emergency use by the World Health Organization (WHO), such as mRNA-1273 by Moderna, BNT162b2 by Pfizer/BioNTech, Ad26.COV2.S by Janssen, AZD1222 by Oxford/AstraZeneca, Covishield by the Serum Institute of India, BBIBP-CorV by Sinopharm, coronaVac by Sinovac, and Covaxin by Bharat Biotech, and the first US Food and Drug Administration-approved antiviral drug Veklury (remdesivir) for the treatment of COVID-19. Several waves of COVID-19 have already occurred worldwide, and good-quality vaccines and medicines should be available for ongoing as well as upcoming waves of the pandemic. Therefore, in silico studies have become an excellent tool for identifying possible ligands that could lead to the development of safer medicines or vaccines. Various phytoconstituents from plants and herbs with antiviral properties are studied further to obtain inhibitors of SARS-CoV-2. In silico screening of various molecular databases like PubChem, ZINC, Asinex Biol-Design Library, and so on has been performed extensively for finding effective ligands against targets. Herein, in silico studies carried out by various researchers are summarized so that one can easily find the best molecule for further in vitro and in vivo studies.

| S-EPMC9073995 | biostudies-literature

Plant Metabolites as SARS-CoV-2 Inhibitors Candidates: In Silico and In Vitro Studies.

Project description:Since it acquired pandemic status, SARS-CoV-2 has been causing all kinds of damage all over the world. More than 6.3 million people have died, and many cases of sequelae are in survivors. Currently, the only products available to most of the world's population to fight the pandemic are vaccines, which still need improvement since the number of new cases, admissions into intensive care units, and deaths are again reaching worrying rates, which makes it essential to compounds that can be used during infection, reducing the impacts of the disease. Plant metabolites are recognized sources of diverse biological activities and are the safest way to research anti-SARS-CoV-2 compounds. The present study computationally evaluated 55 plant compounds in five SARS-CoV-2 targets such Main Protease (Mpro or 3CL or MainPro), RNA-dependent RNA polymerase (RdRp), Papain-Like Protease (PLpro), NSP15 Endoribonuclease, Spike Protein (Protein S or Spro) and human Angiotensin-converting enzyme 2 (ACE-2) followed by in vitro evaluation of their potential for the inhibition of the interaction of the SARS-CoV-2 Spro with human ACE-2. The in silico results indicated that, in general, amentoflavone, 7-O-galloylquercetin, kaempferitrin, and gallagic acid were the compounds with the strongest electronic interaction parameters with the selected targets. Through the data obtained, we can demonstrate that although the indication of individual interaction of plant metabolites with both Spro and ACE-2, the metabolites evaluated were not able to inhibit the interaction between these two structures in the in vitro test. Despite this, these molecules still must be considered in the research of therapeutic agents for treatment of patients affected by COVID-19 since the activity on other targets and influence on the dynamics of viral infection during the interaction Spro x ACE-2 should be investigated.

| S-EPMC9501068 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data