Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SARS-CoV-2: An Update on Potential Antivirals in Light of SARS-CoV Antiviral Drug Discoveries.

ABSTRACT: Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases are Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and Middle East Respiratory Syndrome-CoV (MERS-CoV). Both viruses resulted in hundreds of deaths after spreading to several countries. Most recently, SARS-CoV-2 has emerged as the third HCoV causing severe respiratory distress syndrome and viral pneumonia (known as COVID-19) in patients from Wuhan, China, in December 2019. Soon after its discovery, SARS-CoV-2 spread to all countries, resulting in millions of cases and thousands of deaths. Since the emergence of SARS-CoV, many research groups have dedicated their resources to discovering effective antivirals that can treat such life-threatening infections. The rapid spread and high fatality rate of SARS-CoV-2 necessitate the quick discovery of effective antivirals to control this outbreak. Since SARS-CoV-2 shares 79% sequence identity with SARS-CoV, several anti-SARS-CoV drugs have shown promise in limiting SARS-CoV-2 replication in vitro and in vivo. In this review, we discuss antivirals described for SARS-CoV and provide an update on therapeutic strategies and antivirals against SARS-CoV-2. The control of the current outbreak will strongly depend on the discovery of effective and safe anti-SARS-CoV-2 drugs.

SUBMITTER: Elshabrawy HA

PROVIDER: S-EPMC7350231 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

On Drug-Membrane Permeability of Antivirals for SARS-CoV-2.

Project description:One of the key parameters required to identify effective drugs is membrane permeability, as a compound intended for an intracellular target with poor permeability will have low efficacy. In this paper, we leverage a computational approach recently developed by our group to study the interactions between nanoparticles and mammalian membranes to study the time of entry of a variety of drugs into the viral envelope of coronavirus as well as cellular organelles. Using a combination of all-atoms molecular dynamics simulations and statistical analysis, we consider both drug characteristics and membrane properties to determine the behavior of 79 drugs and their interactions with the viral envelope, composed of the membrane and spike protein, as well as five other membranes that correspond to various mammalian compartments (lysosome, plasma, Golgi, mitochondrial, and endoplasmic reticulum membranes). The results highlight important trends that can be exploited for drug design, from the relatively high permeability of the viral envelope and the effect of transmembrane proteins, to the differences in permeability between organelles. When compared with bioavailability data present in the literature, the model results suggest a negative correlation between time of permeation and bioavailability of promising drugs. The method is general and flexible and can be employed for a variety of molecules, from small drugs to small nanoparticles, as well to a variety of biological membranes. Overall, the results indicate that this model can contribute to the identification of successful drugs as it predicts the ability of compounds to reach both intended and unintended intracellular targets.

| S-EPMC7860140 | biostudies-literature

Insights into SARS-CoV-2 evolution, potential antivirals, and vaccines.

Project description:SARS-CoV-2 is a novel coronavirus, spread among humans, and to date, more than 100 million of laboratory-confirmed cases have been reported worldwide. The virus demonstrates 96% similarity to a coronavirus from a horseshoe bat and most probably emerged from a spill over from bats or wild animal(s) to humans. Currently, two variants are circulating in the UK and South Africa and spread to many countries around the world. The impact of mutations on virus replication, virulence and transmissibility should be monitored carefully. Current data suggest recurrent infection with SARS-CoV-2 correlated to the level of neutralising antibodies and with sustained memory responses following infection. Recently, remdesivir was FDA approved for treatment of COVID-19, however many potential antivirals are currently in different clinical trials. Clinical data and experimental studies indicated that licenced vaccines are helpful in controlling the disease. However, the current vaccines should be evaluated against the emerging variants of SARS-CoV-2.

| S-EPMC7898979 | biostudies-literature

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2.

Project description:Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.

| S-EPMC8587465 | biostudies-literature

Potential Antiviral Options against SARS-CoV-2 Infection.

Project description:As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.

| S-EPMC7354438 | biostudies-literature

Identification of potential antivirals against SARS-CoV-2 using virtual screening method.

Project description:SARS-CoV-2 has triggered a major epidemic among people around the world, and it is the newest in the sequence to become prevalent among other infectious diseases. The drug repurposing concept has been utilized effectively for numerous viral infections. Considering the situation and the urgency, the idea of drug repurposing for coronavirus infection (COVID-19) is also being studied. The molecular docking method was used for the screening of 29 antiviral drugs against primary protease proteins (MPP) of SARS-CoV-2, spike ecto-domain, spike receptor binding domain, Nsp9 RNA binding protein, and HR2 domain. Among these drugs, in terms of least binding energy, Indinavir, Sorivudine, Cidofovir, and Darunavir showed minimum docking scores with all the key proteins. For ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analysis, the ADMET properties of the top 4 drug candidates were retrieved through literature study. This analysis revealed that these drug candidates are well metabolized, distributed, and bioavailable, but have some undesirable effects. Furthermore, some approved structural analogues, such as Telbivudine, Tenofovir, Amprenavir, Fosamprenavir, etc., were predicted as similar drugs which may also be used for treating viral infections. We highly recommend these drug candidates as potential fighters against the deadly SARS-CoV-2 virus, and suggest in vivo trials for experimental validation of our findings.

| S-EPMC7874919 | biostudies-literature

SARS-CoV-2-host proteome interactions for antiviral drug discovery.

Project description:Treatment options for COVID-19, caused by SARS-CoV-2, remain limited. Understanding viral pathogenesis at the molecular level is critical to develop effective therapy. Some recent studies have explored SARS-CoV-2-host interactomes and provided great resources for understanding viral replication. However, host proteins that functionally associate with SARS-CoV-2 are localized in the corresponding subnetwork within the comprehensive human interactome. Therefore, constructing a downstream network including all potential viral receptors, host cell proteases, and cofactors is necessary and should be used as an additional criterion for the validation of critical host machineries used for viral processing. This study applied both affinity purification mass spectrometry (AP-MS) and the complementary proximity-based labeling MS method (BioID-MS) on 29 viral ORFs and 18 host proteins with potential roles in viral replication to map the interactions relevant to viral processing. The analysis yields a list of 693 hub proteins sharing interactions with both viral baits and host baits and revealed their biological significance for SARS-CoV-2. Those hub proteins then served as a rational resource for drug repurposing via a virtual screening approach. The overall process resulted in the suggested repurposing of 59 compounds for 15 protein targets. Furthermore, antiviral effects of some candidate drugs were observed in vitro validation using image-based drug screen with infectious SARS-CoV-2. In addition, our results suggest that the antiviral activity of methotrexate could be associated with its inhibitory effect on specific protein-protein interactions.

| S-EPMC8552907 | biostudies-literature

Repurposing an Antiviral Drug against SARS-CoV-2 Main Protease.

Project description:This article highlights recent pioneering work by Günther et al. towards the discovery of potential repurposed antiviral compounds (peptidomimetic and non-peptidic) against the SARS-CoV-2 main protease (Mpro ). The antiviral activity of the most potent drugs is discussed along with their binding mode to Mpro as observed through X-ray crystallographic screening.

| S-EPMC8652770 | biostudies-literature

Spike protein recognizer receptor ACE2 targeted identification of potential natural antiviral drug candidates against SARS-CoV-2.

Project description:Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. Most of the ACE2 inhibitors discovered till now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals' inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a 3D structure-based-pharmacophore model (SBPM) has been developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based on their binding affinity (-7.5, -7.1, -7.1, and -7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell.

| S-EPMC8474879 | biostudies-literature

Drug repurposing based on a Quantum-Inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 including vitamin B12.

Project description:The COVID-19 pandemic has accelerated the need to identify new therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir (RDV), the only antiviral against SARS-CoV-2 currently approved for human use, using a quantum-inspired device. We modelled RDV and compounds present in the DrugBank database as graphs, established the optimal parameters in our algorithm and resolved the Maximum Weighted Independent Set problem within the conflict graph generated. We also employed a traditional Tanimoto fingerprint model. The two methods yielded different lists of compounds, with some overlap. While GS-6620 was the top compound predicted by both models, the QUBO model predicted BMS-986094 as second best. The Tanimoto model predicted different forms of cobalamin, also known as vitamin B12. We then determined the half maximal inhibitory concentration (IC 50 ) values in cell culture models of SARS-CoV-2 infection and assessed cytotoxicity. Lastly, we demonstrated efficacy against several variants including SARS-CoV-2 Strain England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). Our data reveal that BMS-986094 and different forms of vitamin B12 are effective at inhibiting replication of all these variants of SARS-CoV-2. While BMS-986094 can cause secondary effects in humans as established by phase II trials, these findings suggest that vitamin B12 deserves consideration as a SARS-CoV-2 antiviral, particularly given its extended use and lack of toxicity in humans, and its availability and affordability. Our screening method can be employed in future searches for novel pharmacologic inhibitors, thus providing an approach for accelerating drug deployment.

| S-EPMC8366797 | biostudies-literature

Phytochemicals against SARS-CoV as potential drug leads.

Project description:The newly emerged SARS-CoV-2 strains from the coronavirus (CoV) family is causing one of the most disruptive pandemics of the past century. Developing antiviral drugs is a challenge for the scientific community and pharmaceutical industry. Given the health emergency, repurposing of existing antiviral, antiinflammatory or antimalarial drugs is an attractive option for controlling SARS-CoV-2 with drugs. However, phytochemicals selected based on ethnomedicinal information as well as in vitro antiviral studies could be promising as well. Here, we summarise the phytochemicals with reported anti-CoV activity, and further analyzed them computationally to accelerate validation for drug development against SARS-CoV-2. This systematic review started from the most potent phytocompounds (IC50 in μM) against SARS-CoV, followed by a cluster analysis to locate the most suitable lead(s). The advanced molecular docking used the crystallography structure of SARS-CoV-2-cysteine-like protease (SARS-CoV-2-3CLpro) as a target. In total, seventy-eight phytochemicals with anti-CoV activity against different strains in cellular assays, were selected for this computational study, and compared with two existing repurposed FDA-approved drugs: lopinavir and ritonavir. This review brings insights in the potential application of phytochemicals and their derivatives, which could guide researchers to develop safe drugs against SARS-CoV-2.

| S-EPMC7726715 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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