Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In silico studies on phytochemicals to combat the emerging COVID-19 infection

ABSTRACT: The current COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, remains a serious health hazard globally. The SARS-CoV-2 Mpro and spike proteins, as well as the human ACE2 receptor, have previously been reported as good targets for the development of new drug leads to combat COVID-19. Various ligands, including synthetic and plant-derived small molecules, can interact with the aforementioned proteins. In this study, we investigated the interaction of eight phytochemicals, from selected medicinal plants (Aegle marmelos, Azadirachta indica, and Ocimum sanctum) commonly used in Indian traditional medicine, with SARS-CoV-2 Mpro (PDBID: 6LU7), SARS-CoV-2S spike protein (PDB ID: 6M0J) and the human ACE2 receptor (PDB ID: 6M18). All compounds were subjected to density functional theory (DFT) and frontier molecular orbitals (FMO) analysis to determine their geometry, and key electronic and energetic properties. Upon examining the interactions of the phytochemicals with the human ACE2 receptor and the SARS-CoV-2 Mpro, spike protein targets, two compounds (C-5 and C-8) were identified as the best binding ligands. These were further examined in MD simulation studies to determine the stability of the ligand–protein interactions. QSAR, pharmacokinetic and drug-likeness properties studies revealed that C-5 may be the best candidate to serve as a template for the design and development of new drugs to combat COVID-19.

SUBMITTER: Abdalla M

PROVIDER: S-EPMC8523303 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Promising phytochemicals of traditional Indian herbal steam inhalation therapy to combat COVID-19 - An in silico study.

Project description:BackgroundCOVID-19, the presently prevailing global public health emergency has culminated in international instability in economy. This unprecedented pandemic outbreak pressingly necessitated the trans-disciplinary approach in developing novel/new anti-COVID-19 drugs especially, small molecule inhibitors targeting the seminal proteins of viral etiological agent, SARS-CoV-2.MethodsBased on the traditional medicinal knowledge, we made an attempt through molecular docking analysis to explore the phytochemical constituents of three most commonly used Indian herbs in 'steam inhalation therapy' against well recognized viral receptor proteins.ResultsA total of 57 phytochemicals were scrutinized virtually against four structural protein targets of SARS-CoV-2 viz. 3CLpro, ACE-2, spike glycoprotein and RdRp. Providentially, two bioactives from each of the three plants i.e. apigenin-o-7-glucuronide and ellagic acid from Eucalyptus globulus; eudesmol and viridiflorene from Vitex negundo and; vasicolinone and anisotine from Justicia adhatoda were identified to be the best hit lead molecules based on interaction energies, conventional hydrogen bonding numbers and other non-covalent interactions. On comparison with the known SARS-CoV-2 protease inhibitor -lopinavir and RdRp inhibitor -remdesivir, apigenin-o-7-glucuronide was found to be a phenomenal inhibitor of both protease and polymerase, as it strongly interacts with their active sites and exhibited remarkably high binding affinity. Furthermore, in silico drug-likeness and ADMET prediction analyses clearly evidenced the usability of the identified bioactives to develop as drug against COVID-19.ConclusionOverall, the data of the present study exemplifies that the phytochemicals from selected traditional herbs having significance in steam inhalation therapy would be promising in combating COVID-19.

| S-EPMC7780060 | biostudies-literature

An update on emerging therapeutics to combat COVID-19.

Project description:BackgroundThe COVID-19 pandemic has demanded effective therapeutic protocol from researchers and clinicians across the world. Currently, a large amount of primary data have been generated from several preclinical studies. At least 300 clinical trials are underway for drug repurposing against COVID-19; the clinician needs objective evidence-based medication to treat COVID-19.ObservationsSingle-stranded RNA viral genome of SARS-CoV-2 encodes structural proteins (spike protein), non-structural enzymatic proteins (RNA-dependent RNA polymerase, helicase, papain-like protease, 3-chymotrypsin-like protease) and other accessory proteins. These four enzymatic proteins on spike protein are rate-limiting steps in viral replications and, therefore, an attractive target for drug development against SARS-CoV-2. In silico and in vitro studies have identified various potential epitomes as candidate sequences for vaccine development. These studies have also revealed potential targets for drug development and drug repurposing against COVID-19. Clinical trials utilizing antiviral drugs and other drugs have given inconclusive results regarding their clinical efficacy and side effects. The need for angiotensin-converting enzyme (ACE-2) inhibitors/angiotensin receptor blockers and corticosteroids has been recommended. Western countries have adopted telemedicine as an alternative to prevent transmission of infection in the population. Currently, no proven, evidence-based therapeutic regimen exists for COVID-19.ConclusionThe COVID-19 pandemic has put tremendous pressure on researchers to evaluate and approve drugs effective against the disease. Well-controlled randomized trials should assess medicines that are not marketed with substantial evidence of safety and efficacy and more emphasis on time tested approaches for drug evaluation.

| S-EPMC8239852 | biostudies-literature

Cohort survey of healthcare workers with COVID-19 infection

Project description: Not available

| S-BSST563 | biostudies-other

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19.

Project description:COVID-19 and its causative organism SARS-CoV2 that emerged from Wuhan city, China have paralyzed the world. With no clinically approved drugs, the global health system is struggling to find an effective treatment measure. At this crucial juncture, screening of plant-derived compounds may be an effective strategy to combat COVID-19. The present study investigated the binding affinity of phytocompounds with 3-Chymotrypsin-like (3CLpro) and Papain-like proteases (PLpro) of SARS-CoV2 using in-silico techniques. A total of 32 anti-protease phytocompounds were investigated for the binding affinity to the proteins. Docking was performed in Autodock Vina. Pharmacophore descriptors of best ligands were studied using LigandScout. Molecular dynamics (MD) simulation of apo-protein and ligand-bound complexes was carried out in YASARA software. The druglikeness properties of phytocompounds were studied using ADMETlab. Out of 32 phytochemicals, amentoflavone and gallocatechin gallate showed the best binding affinity to 3CLpro (-9.4 kcal/mol) and PLpro (-8.8 kcal/mol). Phytochemicals such as savinin, theaflavin-3,3-digallate, and kazinol-A also showed strong affinity. MD simulation revealed ligand-induced conformational changes in the protein with decreased surface area and higher stability. The RMSD/F of proteins and ligands showed stability of the protein suggesting the effective binding of the ligand in both the proteins. Both amentoflavone and gallocatechin gallate possess promising druglikeness property. The present study thus suggests that Amentoflavone and Gallocatechin gallate may be potential inhibitors of 3CLpro and PLpro proteins and effective drug candidates for SARS-CoV2. However, the findings of in silico study need to be supported by in vivo studies to establish the exact mode of action. Communicated by Ramaswamy H. Sarma.

| S-EPMC7594184 | biostudies-literature

Emerging Therapeutic Approaches to Combat COVID-19: Present Status and Future Perspectives.

Project description:Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.

| S-EPMC7983051 | biostudies-literature

Emerging treatment strategies for COVID-19 infection.

Project description:The new type of coronavirus (COVID-19), SARS-CoV-2 originated from Wuhan, China and has led to a worldwide pandemic. COVID-19 is a novel emerging infectious disease caused by SARS-CoV-2 characterized as atypical pneumonia. As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. The typical manifestations of COVID-19 include fever, sore throat, fatigue, cough, and dyspnoea combined with recent exposure. Most of the patients with COVID-19 have mild or moderate disease, however up to 5-10% present with severe and even life-threatening disease course. The mortality rates are approximately 2%. Therefore, there is an urgent need for effective and specific antiviral treatment. Currently, supportive care measures such as ventilation oxygenation and fluid management remain the standard of care. Several clinical trials are currently trying to identify the most potent drug or combination against the disease, and it is strongly recommended to enroll patients into ongoing trials. Antivirals can be proven as safe and effective only in the context of randomized clinical trials. Currently several agents such as chloroquine, hydroxychloroquine, favipiravir, monoclonal antibodies, antisense RNA, corticosteroids, convalescent plasma and vaccines are being evaluated. The large numbers of therapeutic interventions aim to define the most efficacious regimen. The aim of this article is to describe the treatment strategies that have been used for COVID-19 patients and review all the available literature.

| S-EPMC7598940 | biostudies-literature

Decreased memory B cells frequencies in COVID-19 Delta variant vaccine breakthrough infection

Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.

| S-SCDT-EMM-2021-15227 | biostudies-other

Nano-based approach to combat emerging viral (NIPAH virus) infection.

Project description:Emergence of new virus and their heterogeneity are growing at an alarming rate. Sudden outburst of Nipah virus (NiV) has raised serious question about their instant management using conventional medication and diagnostic measures. A coherent strategy with versatility and comprehensive perspective to confront the rising distress could perhaps be effectuated by implementation of nanotechnology. But in concurrent to resourceful and precise execution of nano-based medication, there is an ultimate need of concrete understanding of the NIV pathogenesis. Moreover, to amplify the effectiveness of nano-based approach in a conquest against NiV, a list of developed nanosystem with antiviral activity is also a prerequisite. Therefore the present review provides a meticulous cognizance of cellular and molecular pathogenesis of NiV. Conventional as well several nano-based diagnosis experimentations against viruses have been discussed. Lastly, potential efficacy of different forms of nano-based systems as convenient means to shield mankind against NiV has also been introduced.

| S-EPMC7106268 | biostudies-literature

Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach.

Project description:A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein. The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. The S1 and S2 domains of spike proteins were analyzed, and two vaccine constructs were prioritized with T-cell and B-cell epitopes. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4.

| S-EPMC7365865 | biostudies-literature

Emerging strategies on in silico drug development against COVID-19: challenges and opportunities.

Project description:The importance of coronaviruses as human pathogen has been highlighted by the recent outbreak of SARS-CoV-2 leading to the search of suitable drugs to overcome respiratory infections caused by the virus. Due to the lack of specific drugs against coronavirus, the existing antiviral and antimalarial drugs are currently being administered to the patients infected with SARS-CoV-2. The scientists are also considering repurposing of some of the existing drugs as a suitable option in search of effective drugs against coronavirus till the establishment of a potent drug and/or vaccine. Computer-aided drug discovery provides a promising attempt to enable scientists to develop new and target specific drugs to combat any disease. The discovery of novel targets for COVID-19 using computer-aided drug discovery tools requires knowledge of the structure of coronavirus and various target proteins present in the virus. Targeting viral proteins will make the drug specific against the virus, thereby, increasing the chances of viral mortality. Hence, this review provides the structure of SARS-CoV-2 virus along with the important viral components involved in causing infection. It also focuses on the role of various target proteins in disease, the mechanism by which currently administered drugs act against the virus and the repurposing of few drugs. The gap arising from the absence of specific drugs is addressed by proposing potential antiviral drug targets which might provide insights into structure-based drug development against SARS-CoV-2.

| S-EPMC7438372 | 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