Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the worldwide spread of coronavirus disease 19 (COVID-19), and till now, it has caused death to more than 6.2 million people. Although various vaccines and drug candidates are being tested globally with limited to moderate success, a comprehensive therapeutic cure is yet to be achieved. In this study, we applied computational drug repurposing methods complemented with the analyses of the already existing gene expression data to find better therapeutics in treatment and recovery. Primarily, we identified the most crucial proteins of SARS-CoV-2 and host human cells responsible for viral infection and host response. An in-silico screening of the existing drugs was performed against the crucial proteins for SARS-CoV-2 infection, and a few existing drugs were shortlisted. Further, we analyzed the gene expression data of SARS-CoV-2 in human lung epithelial cells and investigated the molecules that can reverse the cellular mRNA expression profiles in the diseased state. LINCS L1000 and Comparative Toxicogenomics Database (CTD) were utilized to obtain two sets of compounds that can be used to counter SARS-CoV-2 infection from the gene expression perspective. Indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), and Vitamin-A were found in two sets of compounds, and in the in-silico screening of existing drugs to treat SARS-CoV-2. Our in-silico findings on Indomethacin were further successfully validated by in-vitro testing in Vero CCL-81 cells with an IC₅₀ of 12 μM. Along with these findings, we briefly discuss the possible roles of Indomethacin and Vitamin-A to counter the SARS-CoV-2 infection in humans.

SUBMITTER: Chakraborty R

PROVIDER: S-EPMC9245396 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods.

Project description:The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry, followed by the experimental evaluation of the antiviral activity of selected compounds, has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry-cepharantine, clofazimine, metergoline, imatinib and efloxate-have been identified.

| S-EPMC8067418 | biostudies-literature

Antiviral Activity of Two Marine Carotenoids against SARS-CoV-2 Virus Entry In Silico and In Vitro.

Project description:The marine carotenoids fucoxanthin and siphonaxanthin are powerful antioxidants that are attracting focused attention to identify a variety of health benefits and industry applications. In this study, the binding energy of these carotenoids with the SARS-CoV-2 Spike-glycoprotein was predicted by molecular docking simulation, and their inhibitory activity was confirmed with SARS-CoV-2 pseudovirus on HEK293 cells overexpressing angiotensin-converting enzyme 2 (ACE2). Siphonaxanthin from Codium fragile showed significant antiviral activity with an IC50 of 87.4 μM against SARS-CoV-2 pseudovirus entry, while fucoxanthin from Undaria pinnatifida sporophyll did not. The acute toxicities were predicted to be relatively low, and pharmacokinetic predictions indicate GI absorption. Although further studies are needed to elucidate the inhibition of viral infection by siphonaxanthin, these results provide useful information in the application of these marine carotenoids for the treatment and prevention of COVID-19.

| S-EPMC8235185 | biostudies-literature

In silico evidence of beauvericin antiviral activity against SARS-CoV-2.

Project description:BackgroundScientists are still battling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus 2019 (COVID-19) pandemic so human lives can be saved worldwide. Secondary fungal metabolites are of intense interest due to their broad range of pharmaceutical properties. Beauvericin (BEA) is a secondary metabolite produced by the fungus Beauveria bassiana. Although promising anti-viral activity has previously been reported for BEA, studies investigating its therapeutic potential are limited.MethodsThe objective of this study was to assess the potential usage of BEA as an anti-viral molecule via protein-protein docking approaches using MolSoft.ResultsIn-silico results revealed relatively favorable binding energies for BEA to different viral proteins implicated in the vital life stages of this virus. Of particular interest is the capability of BEA to dock to both the main coronavirus protease (Pockets A and B) and spike proteins. These results were validated by molecular dynamic simulation (Gromacs). Several parameters, such as root-mean-square deviation/fluctuation, the radius of gyration, H-bonding, and free binding energy were analyzed. Computational analyses revealed that interaction of BEA with the main protease pockets in addition to the spike glycoprotein remained stable.ConclusionAltogether, our results suggest that BEA might be considered as a potential competitive and allosteric agonist inhibitor with therapeutic options for treating COVID-19 pending in vitro and in vivo validation.

| S-EPMC8709726 | biostudies-literature

In Vitro Antiviral Activity of Nordihydroguaiaretic Acid against SARS-CoV-2.

Project description:The coronavirus infectious disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been spreading rapidly worldwide, creating a pandemic. This article describes the evaluation of the antiviral activity of nordihydroguaiaretic acid (NDGA), a molecule found in Creosote bush (Larrea tridentata) leaves, against SARS-CoV-2 in vitro. A 35 µM concentration of NDGA was not toxic to Vero cells and exhibited a remarkable inhibitory effect on the SARS-CoV-2 cytopathic effect, viral plaque formation, RNA replication, and expression of the SARS-CoV-2 spike glycoprotein. The 50% effective concentration for NDGA was as low as 16.97 µM. Our results show that NDGA could be a promising therapeutic candidate against SARS-CoV-2.

| S-EPMC10222355 | biostudies-literature

In-silico screening of naturally derived phytochemicals against SARS-CoV Main protease.

Project description:Coronavirus disease 2019 (COVID-19) is a rapidly growing pandemic that requires urgent therapeutic intervention. Finding potential anti COVID-19 drugs aside from approved vaccines is progressively going on. The chemically diverse natural products represent valuable sources for drug leads. In this study, we aimed to find out safe and effective COVID-19 protease inhibitors from a library of natural products which share the main nucleus/skeleton of FDA-approved drugs that were employed in COVID-19 treatment guidelines or repurposed by previous studies. Our library was subjected to virtual screening against SARS-CoV Main protease (Mpro) using Molecular Operating Environment (MOE) software. Twenty-two out of those natural candidates showed higher binding scores compared to their analogues. We repurpose these natural products including alkaloids, glucosinolates, and phenolics as potential platforms for the development of anti-SARS-CoV-2 therapeutics. This study paves the way towards discovering a lead used in the treatment of COVID-19 from natural sources and introduces phytomedicines with dual therapeutic effects against COVID-19 besides their original pharmacological effects. We recommend further in vitro evaluation of their anti-COVID-19 activity and future clinical studies.

| S-EPMC8638226 | biostudies-literature

Novel immunomodulatory properties of adenosine analogs promote their antiviral activity against SARS-CoV-2

Project description:The COVID-19 pandemic reminded us of the urgent need for new antivirals to control emerging infectious diseases and potential future pandemics. Immunotherapy has revolutionized oncology and could complement the use of antivirals, but its application to infectious diseases remains largely unexplored. Nucleoside analogs are a class of agents widely used as antiviral and anti-neoplastic drugs. Their antiviral activity is generally based on interference with viral nucleic acid replication or transcription. Based on our previous work and computer modeling, we hypothesize that antiviral adenosine analogs, like remdesivir, have previously unrecognized immunomodulatory properties which contribute to their therapeutic activity. In the case of remdesivir, we show that these properties are due to its metabolite, GS-441524, acting as an Adenosine A2A Receptor antagonist. Our findings support a new rationale for the design of next-generation antiviral agents with dual - immunomodulatory and intrinsic - antiviral properties. These compounds could represent game-changing therapies to control emerging viral diseases and future pandemics.

| S-SCDT-10_1038-S44319-024-00189-4 | biostudies-other

A functional assay for serum detection of antibodies against SARS-CoV-2 nucleoprotein

Project description:The humoral immune response to SARS-CoV-2 results in antibodies against spike (S) and nucleoprotein (N). However, whilst there are widely-available neutralization assays for S-antibodies, there is no assay for N-antibody activity. Here we present a simple in vitro method called EDNA (electroporated-antibody dependent neutralization assay) that provides a quantitative measure of N-antibody activity in unpurified serum from SARS-CoV-2 convalescents. We show that N-antibodies neutralize SARS-CoV-2 intracellularly and cell-autonomously but require the cytosolic Fc-receptor TRIM21. Using EDNA, we show that low N-antibody titres can be neutralizing, whilst some convalescents possess serum with high titres but weak activity. N-antibody and N-specific T cell activity correlates within individuals, suggesting N-antibodies may protect against SARS-CoV-2 by promoting antigen presentation. This work highlights the potential benefits of N-based vaccines and provides an in vitro assay to allow the antibodies they induce to be tested.

| S-SCDT-EMBOJ-2021-108588 | biostudies-other

Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2.

Project description:The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2][C1SO3]2 and [HCQH2][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2][SO4]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2][GlcCOO]2. Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra- and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.

| S-EPMC9031298 | biostudies-literature

Potential antiviral properties of antiplatelet agents against SARS-CoV-2 infection: an in silico perspective.

Project description:SARS-CoV-2 represents the causative agent of the current pandemic (COVID-19). The drug repurposing technique is used to search for possible drugs that can bind to SARS-CoV-2 proteins and inhibit viral replication. In this study, the FDA-approved antiplatelets are tested against the main protease and spike proteins of SARS-CoV-2 using in silico methods. Molecular docking and molecular dynamics simulation are used in the current study. The results suggest the effectiveness of vorapaxar, ticagrelor, cilostazol, cangrelor, and prasugrel in binding the main protease (Mpro) of SARS-CoV-2. At the same time, vorapaxar, ticagrelor, and cilostazol are the best binders of the spike protein. Therefore, these compounds could be successful candidates against COVID-19 that need to be tested experimentally.

| S-EPMC8435103 | biostudies-literature

Antiviral Activity of Metabolites from Peruvian Plants against SARS-CoV-2: An In Silico Approach.

Project description:(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.

| S-EPMC8270280 | 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