scholarly journals Fluoxetine Can Inhibit SARS-CoV-2 In Vitro

2021 ◽  
Vol 9 (2) ◽  
pp. 339
Author(s):  
Arthur Dechaumes ◽  
Magloire Pandoua Nekoua ◽  
Sandrine Belouzard ◽  
Famara Sane ◽  
Ilka Engelmann ◽  
...  
Keyword(s):  
Cytopathic Effect ◽  
Limit Of Detection ◽  
Acute Infection ◽  
Treatment Strategies ◽  
Potential Value ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Antiviral Mechanism

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease pandemic, drastically affecting global health and economy. Though the understanding of the disease has improved, fighting the virus remains challenging. One of the strategies is repurposing existing drugs as inhibitors of SARS-CoV-2. Fluoxetine (FLX), a selective serotonin reuptake inhibitor, reportedly inhibits the replication of RNA viruses, especially Coxsackieviruses B (CVB), such as CV-B4 in vitro and in vivo. Therefore, in this study, we investigated the in vitro antiviral activity of FLX against SARS-CoV-2 in a model of acute infection. When 10 μM of FLX was added to SARS-CoV-2-infected Vero E6 cells, the virus-induced cytopathic effect was not observed. In this model, the level of infectious particles in the supernatant was lower than that in controls. The level was below the limit of detection of the assay up to day 3 post-infection when FLX was administered before viral inoculation or simultaneously followed by daily inoculation. In conclusion, FLX can inhibit SARS-CoV-2 in vitro. Further studies are needed to investigate the potential value of FLX to combat SARS-CoV-2 infections, treat SARS-CoV-2-induced diseases, and explain the antiviral mechanism of this molecule to pave way for novel treatment strategies.

scholarly journals Manganese complex [Mn(CO)3(tpa-κ3N)]Br increases antibiotic sensitivity in multidrug resistant Streptococcus pneumoniae

2020 ◽  
Author(s):  
Apostolos Liakopoulos ◽  
Roberto M. La Ragione ◽  
Christoph Nagel ◽  
Ulrich Schatzschneider ◽  
Daniel E. Rozen ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Multidrug Resistance ◽  
Streptococcus Pneumoniae ◽  
Treatment Strategies ◽  
Antibiotic Sensitivity ◽  
Multidrug Resistant ◽  
Novel Treatment ◽  
Novel Treatment Strategies

AbstractThe emergence of multidrug-resistance (MDR) in Streptococcus pneumoniae clones and non-vaccine serotypes is of increasing concern, necessitating the development of novel treatment strategies. Here, we determined the efficacy of the Mn complex [Mn(CO)3(tpa-κ3N)]Br against MDR S. pneumoniae strains. Our data showed that [Mn(CO)3(tpa-κ3N)]Br has in vitro and in vivo antibacterial activity and has the potential to be used in combination with currently available antibiotics to increase their effectiveness against MDR S. pneumoniae.

scholarly journals Molecular mechanisms underpinning sarcomas and implications for current and future therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Victoria Damerell ◽  
Michael S. Pepper ◽  
Sharon Prince
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Cells Of Origin ◽  
Novel Treatment Strategies ◽  
Future Therapy

AbstractSarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but there is now mounting evidence that they originate from mesenchymal stromal/stem cells (MSCs). To identify novel treatment strategies for sarcomas, research in recent years has adopted a mechanism-based search for molecular markers for targeted therapy which has included recapitulating sarcomagenesis using in vitro and in vivo MSC models. This review provides a comprehensive up to date overview of the molecular mechanisms that underpin sarcomagenesis, the contribution of MSCs to modelling sarcomagenesis in vivo, as well as novel topics such as the role of epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs in sarcomagenesis. It also reviews current therapeutic options including ongoing pre-clinical and clinical studies for targeted sarcoma therapy and discusses new therapeutic avenues such as targeting recently identified molecular pathways and key transcription factors.

scholarly journals Efficacy of Guanabenz Combination Therapy against Chronic Toxoplasmosis across Multiple Mouse Strains

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Jennifer Martynowicz ◽  
J. Stone Doggett ◽  
William J. Sullivan
Keyword(s):  
Limit Of Detection ◽  
Acute Infection ◽  
Antagonistic Effect ◽  
Mouse Strains ◽  
Chronic Infections ◽  
Content Type ◽  
Brain Cyst ◽  
The Brain

ABSTRACT Toxoplasma gondii, an obligate intracellular parasite that can cause life-threatening acute disease, differentiates into a quiescent cyst stage to establish lifelong chronic infections in animal hosts, including humans. This tissue cyst reservoir, which can reactivate into an acute infection, is currently refractory to clinically available therapeutics. Recently, we and others have discovered drugs capable of significantly reducing the brain cyst burden in latently infected mice, but not to undetectable levels. In this study, we examined the use of novel combination therapies possessing multiple mechanisms of action in mouse models of latent toxoplasmosis. Our drug regimens included combinations of pyrimethamine, clindamycin, guanabenz, and endochin-like quinolones (ELQs) and were administered to two different mouse strains in an attempt to eradicate brain tissue cysts. We observed mouse strain-dependent effects with these drug treatments: pyrimethamine-guanabenz showed synergistic efficacy in C57BL/6 mice yet did not improve upon guanabenz monotherapy in BALB/c mice. Contrary to promising in vitro results demonstrating toxicity to bradyzoites, we observed an antagonistic effect between guanabenz and ELQ-334 in vivo. While we were unable to completely eliminate the brain cyst burden, we found that a combination treatment with ELQ-334 and pyrimethamine impressively reduced the brain cyst burden by 95% in C57BL/6 mice, which approached the limit of detection. These analyses highlight the importance of evaluating anti-infective drugs in multiple mouse strains and will help inform further preclinical studies of cocktail therapies designed to treat chronic toxoplasmosis.

scholarly journals Antimicrobial activity of a novel bioengineered honey against non-typeable Haemophilus influenzae biofilms: an in vitro study

2018 ◽  
Vol 71 (6) ◽  
pp. 554-558 ◽  
Author(s):  
Rachel S Newby ◽  
Matthew Dryden ◽  
Raymond N Allan ◽  
Rami J Salib
Keyword(s):  
Haemophilus Influenzae ◽  
Treatment Strategies ◽  
In Vitro Study ◽  
Opportunistic Pathogen ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Novel Treatment ◽  
Novel Treatment Strategies

The opportunistic pathogen non-typeable Haemophilus influenzae (NTHi) plays an important role in many chronic respiratory diseases including otitis media, chronic rhinosinusitis, cystic fibrosis and chronic obstructive pulmonary disease. Biofilm formation has been implicated in NTHi colonisation, persistence of infection and recalcitrance towards antimicrobials. There is therefore a pressing need for the development of novel treatment strategies that are effective against NTHi biofilm-associated diseases. SurgihoneyRO is a honey-based product that has been bioengineered to enable the slow release of H2O2, a reactive oxygen species to which H. influenzae is susceptible. Treatment of established NTHi biofilms with SurgihoneyRO significantly reduced biofilm viability through enhanced H2O2 production and was shown to be more effective than the conventional antibiotic co-amoxiclav.

scholarly journals Therapeutic Effects of Curcumin—From Traditional Past to Present and Future Clinical Applications

2019 ◽  
Vol 20 (15) ◽  
pp. 3757 ◽  
Author(s):  
Beatrice Bachmeier ◽  
Dieter Melchart
Keyword(s):  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Scientific Evidence ◽  
Treatment Strategies ◽  
Therapeutic Effects ◽  
Microbial Infection ◽  
Therapeutic Benefits ◽  
Novel Treatment Strategies

The efficacy of the plant-derived polyphenol curcumin, in various aspects of health and wellbeing, is matter of public interest. An internet search of the term “Curcumin” displays about 12 million hits. Among the multitudinous information presented on partly doubtful websites, there are reports attracting the reader with promises ranging from eternal youth to cures for incurable diseases. Unfortunately, many of these reports are not based on scientific evidence, but they feed the desideratum of the reader for a “miracle cure”. This circumstance makes it very difficult for researchers, who work in a scientifically sound and evidence-based manner on the therapeutic benefits (or side effects) of curcumin, to demarcate their results from sensational reports that circulate in the web and in other media. This is only one of many obstacles making it difficult to pave curcumin’s way into clinical application; others are its nonpatentability and low economic usability. A further impediment comes from scientists who never worked with curcumin or any other natural plant-derived compound in their own labs. They have never tested these compounds in any scientific assay, neither in vitro nor in vivo; however, they claim, in a sometimes polemic manner, that everything that has so far been published on curcumin’s molecular effects is based on artefacts. The here presented Special Issue comprises a collection of five scientifically sound articles and nine reviews reporting on the therapeutic benefits and the molecular mechanisms of curcumin or of chemically modified curcumin in various diseases ranging from malignant tumors to chronic diseases, microbial infection, and even neurodegenerative diseases. The excellent results of the scientific projects that underlie the five original papers give reason to hope that curcumin will be part of novel treatment strategies in the near future—either as monotherapy or in combination with other drugs or therapeutic applications.

scholarly journals Astodrimer sodium, dendrimer antiviral, inhibits replication of SARS-CoV-2 in vitro

2020 ◽  
Author(s):  
Jeremy R.A. Paull ◽  
Alex Castellarnau ◽  
Carolyn A. Luscombe ◽  
Jacinth K. Fairley ◽  
Graham P. Heery
Keyword(s):  
Antiviral Activity ◽  
Host Cell ◽  
Cytopathic Effect ◽  
Limit Of Detection ◽  
Antiviral Agent ◽  
Effective Response ◽  
Enveloped Viruses ◽  
Host Cell Interactions

AbstractAn effective response to the ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will require a range of complementary preventive modalities. The current studies were conducted to evaluate the in vitro SARS-CoV-2 antiviral activity of astodrimer sodium, a dendrimer with broad spectrum antimicrobial activity, including against enveloped viruses in in vitro and in vivo models, that is marketed for antiviral and antibacterial applications. We report that astodrimer sodium inhibits replication of SARS-CoV-2 in Vero E6 cells when added to cells 1-hour prior to or 1-hour post infection, with 50% effective concentrations reducing virus-induced cytopathic effect (EC50) ranging from 0.090 to 0.742 μM (0.002 to 0.012 mg/mL). The selectivity index (SI) in these assays was as high as 2197. Astodrimer sodium was also effective in a virucidal evaluation when mixed with virus for 1 hour prior to infection of cells (EC50 1.83 μM [0.030 mg/mL]). Results from a time of addition study, which showed infectious virus was below the lower limit of detection at all time points tested, were consistent with the compound inhibiting early virus entry steps. The data were similar for all investigations and were consistent with the potent antiviral activity of astodrimer sodium being due to inhibition of virus-host cell interactions, as previously demonstrated for other viruses. Further studies will confirm if astodrimer sodium binds to SARS-CoV-2 spike protein and physically blocks initial association of the virus with heparan sulfate proteoglycans on the host cell. Given the in vitro effectiveness and significantly high SI, astodrimer sodium warrants further investigation for potential as a nasally administered or inhaled antiviral agent for SARS-CoV-2 prevention and treatment applications.

scholarly journals Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1979
Author(s):  
Andrea Jess Josiah ◽  
Danielle Twilley ◽  
Sreejarani Kesavan Pillai ◽  
Suprakas Sinha Ray ◽  
Namrita Lall
Keyword(s):  
Cell Carcinoma ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Contributing Factors ◽  
Alternative Approach ◽  
Transdermal Drug Delivery Systems ◽  
Novel Treatment Strategies

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.

scholarly journals The Antitumor Effect of Lipophilic Bisphosphonate BPH1222 in Melanoma Models: The Role of the PI3K/Akt Pathway and the Small G Protein Rheb

2019 ◽  
Vol 20 (19) ◽  
pp. 4917 ◽  
Author(s):  
Rittler ◽  
Baranyi ◽  
Molnár ◽  
Garay ◽  
Jalsovszky ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Pi3k Pathway ◽  
Recent Success ◽  
Apoptotic Effect ◽  
Cancer Types ◽  
Novel Treatment Strategies ◽  
In Vivo Growth

Malignant melanoma is one of the most metastatic cancer types, and despite recent success with novel treatment strategies, there is still a group of patients who do not respond to any therapies. Earlier, the prenylation inhibitor hydrophilic bisphosphonate zoledronic acid (ZA) was found to inhibit melanoma growth in vitro, but only a weaker effect was observed in vivo due to its hydrophilic properties. Recently, lipophilic bisphosphonates (such as BPH1222) were developed. Accordingly, for the first time, we compared the effect of BPH1222 to ZA in eight melanoma lines using viability, cell-cycle, clonogenic and spheroid assays, videomicroscopy, immunoblot, and xenograft experiments. Based on 2D and spheroid assays, the majority of cell lines were more sensitive to BPH. The activation of Akt and S6 proteins, but not Erk, was inhibited by BPH. Additionally, BPH had a stronger apoptotic effect than ZA, and the changes of Rheb showed a correlation with apoptosis. In vitro, only M24met cells were more sensitive to ZA than to BPH; however, in vivo growth of M24met was inhibited more strongly by BPH. Here, we present that lipophilic BPH is more effective on melanoma cells than ZA and identify the PI3K pathway, particularly Rheb as an important mediator of growth inhibition.

scholarly journals Conventional and Novel Treatment Strategies to Combat COVID-19 along with Review of most Affected Countries

2020 ◽  
Vol V (I) ◽  
pp. 25-32
Author(s):  
Umair-Ul-Hassan ◽  
Rana Muhammad Awais Khan ◽  
Shafiq-Ur-Rehman ◽  
Amjad Khan
Keyword(s):  
Viral Genome ◽  
Plasma Proteins ◽  
Treatment Strategies ◽  
Advance Technology ◽  
Novel Technique ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Approved Drugs ◽  
Fda Approved Drugs

This review illustrates a comparison of currently implemented strategies and the need of a novel technique to cure the COVID-19. Current strategies served a lot to cope up with the situation by decreasing the rate of fatalities i.e. some FDA approved drugs and giving immunity by the plasma proteins of cured patients, however these approaches could not eliminate the pandemic from the society emphasizing that some advance technology need to be considered in order to fight with SARS-COV-2 virus. CRISPR-Cas based approach to inactivate the virus before its fusion with host DNA has been successful in in-vitro studies performed at Stanford University along with SHERLOCK & MAMMOTH biosciences who were able to degrade 80 % viral genome. Here we have also done a literature review of major affected countries China, Italy, United states, and India.

scholarly journals Human Stem Cell-Derived GABAergic Interneurons Establish Efferent Synapses onto Host Neurons in Rat Epileptic Hippocampus and Inhibit Spontaneous Recurrent Seizures

2021 ◽  
Vol 22 (24) ◽  
pp. 13243
Author(s):  
Eliška Waloschková ◽  
Ana Gonzalez-Ramos ◽  
Apostolos Mikroulis ◽  
Jan Kudláček ◽  
My Andersson ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Treatment Strategies ◽  
Inhibitory Synapses ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Epileptiform Discharges ◽  
Whole Cell Patch Clamp ◽  
Novel Treatment Strategies

Epilepsy is a complex disorder affecting the central nervous system and is characterised by spontaneously recurring seizures (SRSs). Epileptic patients undergo symptomatic pharmacological treatments, however, in 30% of cases, they are ineffective, mostly in patients with temporal lobe epilepsy. Therefore, there is a need for developing novel treatment strategies. Transplantation of cells releasing γ-aminobutyric acid (GABA) could be used to counteract the imbalance between excitation and inhibition within epileptic neuronal networks. We generated GABAergic interneuron precursors from human embryonic stem cells (hESCs) and grafted them in the hippocampi of rats developing chronic SRSs after kainic acid-induced status epilepticus. Using whole-cell patch-clamp recordings, we characterised the maturation of the grafted cells into functional GABAergic interneurons in the host brain, and we confirmed the presence of functional inhibitory synaptic connections from grafted cells onto the host neurons. Moreover, optogenetic stimulation of grafted hESC-derived interneurons reduced the rate of epileptiform discharges in vitro. We also observed decreased SRS frequency and total time spent in SRSs in these animals in vivo as compared to non-grafted controls. These data represent a proof-of-concept that hESC-derived GABAergic neurons can exert a therapeutic effect on epileptic animals presumably through establishing inhibitory synapses with host neurons.

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