scholarly journals Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials

2021 ◽  
Vol 128 (2) ◽  
pp. 127-169 ◽  
Author(s):  
Wojciech Danysz ◽  
Andrzej Dekundy ◽  
Astrid Scheschonka ◽  
Peter Riederer
Keyword(s):  
Viral Infections ◽  
Therapeutic Potential ◽  
Aromatic Amino Acids ◽  
Disease Symptoms ◽  
Hyperactivity Disorder ◽  
Pharmacological Targets ◽  
Cord Injury ◽  
Sigma 1 ◽  
Therapeutic Doses

AbstractThe aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use to further indications beyond Parkinson’s disease symptoms and viral infections. Considering amantadine’s affinities in vitro and the expected concentration at targets at therapeutic doses in humans, the following primary targets seem to be most plausible: aromatic amino acids decarboxylase, glial-cell derived neurotrophic factor, sigma-1 receptors, phosphodiesterases, and nicotinic receptors. Further three targets could play a role to a lesser extent: NMDA receptors, 5-HT3 receptors, and potassium channels. Based on published clinical studies, traumatic brain injury, fatigue [e.g., in multiple sclerosis (MS)], and chorea in Huntington’s disease should be regarded potential, encouraging indications. Preclinical investigations suggest amantadine’s therapeutic potential in several further indications such as: depression, recovery after spinal cord injury, neuroprotection in MS, and cutaneous pain. Query in the database http://www.clinicaltrials.gov reveals research interest in several further indications: cancer, autism, cocaine abuse, MS, diabetes, attention deficit-hyperactivity disorder, obesity, and schizophrenia.

scholarly journals A narrative review of herbal preparations against RNA viruses

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eghbal Jasemi ◽  
Saeideh Momtaz ◽  
Reza Ghaffarzadegan ◽  
Amir Hossein Abdolghaffari ◽  
Mohammad Abdollahi
Keyword(s):  
Infectious Diseases ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Synthetic Compound ◽  
Novel Approach ◽  
Plant Families ◽  
Approved Drugs ◽  
Almost All

Background: Throughout history, the plant kingdom has been a source of medicine in almost all cultures. Nowadays, ensuring the safety, quality, and effectiveness of medicinal herbs and their products has become an essential issue in industrialized and developing countries. Phytochemicals are usually involved in pharmacological actions and are used worldwide for various purposes, including the treatment of infectious diseases. Objectives: Although several therapeutics were designed to control infectious diseases, viral infections are still fatal. Currently, evidence extracted from in vivo, in vitro, and silico studies support the antiviral activity of many herbs scientifically; however, the therapeutic potential of many other herbs is still unknown. Plants and their products may potentially control the propagation of viruses in a variety of conditions. Methods: Data were extracted from PubMed, Scopus, Google Scholar, and Science Direct from 1983-2020. We gathered a list of plant extracts, phytochemicals, and herbal formulations that can inhibit RNA viral infections, mainly those are originated from the coronaviruses family. We also provided an overview of their inhibitory mechanism of actions. Results: Plant families, including Lamiaceae, Asteraceae, and Myrtaceae, contain the highest number of species with anti-coronaviruses activities, respectively. Conclusion: It can be suggested that the combination of these antiviral ingredients with each other, any synthetic compound, or already approved drugs or inhibitors can be a novel approach for antiviral therapies.  

scholarly journals Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2489
Author(s):  
Aleksandr Ianevski ◽  
Rouan Yao ◽  
Eva Zusinaite ◽  
Laura Sandra Lello ◽  
Sainan Wang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Side Effects ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Clinical Development ◽  
Rna Transcription ◽  
Synthesis And Processing ◽  
Synergistic Combinations

Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα–remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. Conclusions: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.

scholarly journals Synergistic Interferon Alpha-based Drug Combinations Inhibit SARS-CoV-2 and other viral Infections in Vitro

2021 ◽  
Author(s):  
Aleksandr Ianevski ◽  
Rouan Yao ◽  
Eva Zusinaite ◽  
Laura Lello ◽  
Sainan Wang ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Influenza A ◽  
Viral Infections ◽  
Human Lung ◽  
Therapeutic Potential ◽  
A549 Cells ◽  
Drug Dose ◽  
Human Interferon ◽  
Lung Epithelial

Abstract There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. In the present study, we found that recombinant human interferon-alpha (IFNa) triggered cell intrinsic and extrinsic antiviral responses and reduced replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human lung epithelial Calu-3 cells. However, IFNa alone was insufficient to completely abolish SARS-CoV-2 replication. Combinations of IFNa with camostat, remdesivir, EIDD-2801, cycloheximide or convalescent serum showed strong synergy and effectively inhibited SARS-CoV-2 infection. Additionally, we demonstrated synergistic antiviral activity of IFNa2a with pimodivir against influenza A virus (FluAV) infection in human lung epithelial A549 cells, as well as of IFNa2a with lamivudine against human immunodeficiency virus 1 (HIV-1) infection in human TZM-bl cells. Our results indicate that IFNa2a-based combinational therapies help to reduce drug dose and improve efficacy in comparison with monotherapies, making them attractive targets for further pre-clinical and clinical development.

scholarly journals Employing Endogenous NSCs to Promote Recovery of Spinal Cord Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Sumei Liu ◽  
Zhiguo Chen
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Potential ◽  
Central Canal ◽  
Injured Tissue ◽  
Cord Injury ◽  
Heterogeneous Nature ◽  
Adult Hippocampus

Endogenous neural stem cells (NSCs) exist in the central canal of mammalian spinal cords. Under normal conditions, these NSCs remain quiescent and express FoxJ1. After spinal cord injury (SCI), the endogenous NSCs of a heterogeneous nature are activated and proliferate and migrate towards the lesion site and mainly differentiate into astrocytes to repair the injured tissue. In vitro, spinal cord NSCs are multipotent and can differentiate into neurons, astrocytes, and oligodendrocytes. The altered microenvironments after SCI play key roles on the fate determination of activated NSCs, especially on the neuronal specification potential. Studies show that the activated spinal cord NSCs can generate interneurons when transplanted into the adult hippocampus. In addition, the spinal cord NSCs exhibit low immunogenicity in a transplantation context, thus implicating a promising therapeutic potential on SCI recovery. Here, we summarize the characteristics of spinal cord NSCs, especially their properties after injury. With a better understanding of endogenous NSCs under normal and SCI conditions, we may be able to employ endogenous NSCs for SCI repair in the future.

scholarly journals Erythropoietin as a Neuroprotective Molecule: An Overview of Its Therapeutic Potential in Neurodegenerative Diseases

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141987142 ◽  
Author(s):  
Federica Rey ◽  
Alice Balsari ◽  
Toniella Giallongo ◽  
Sara Ottolenghi ◽  
Anna M. Di Giulio ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Erythropoietin Receptor ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Erythroid Progenitor ◽  
Beneficial Effects ◽  
Cord Injury

Erythropoietin (EPO) is a cytokine mainly induced in hypoxia conditions. Its major production site is the kidney. EPO primarily acts on the erythroid progenitor cells in the bone marrow. More and more studies are highlighting its secondary functions, with a crucial focus on its role in the central nervous system. Here, EPO may interact with up to four distinct isoforms of its receptor (erythropoietin receptor [EPOR]), activating different signaling cascades with roles in neuroprotection and neurogenesis. Indeed, the EPO/EPOR axis has been widely studied in the neurodegenerative diseases field. Its potential therapeutic effects have been evaluated in multiple disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injury, as well as brain ischemia, hypoxia, and hyperoxia. EPO is showing great promise by counteracting secondary neuroinflammatory processes, reactive oxygen species imbalance, and cell death in these diseases. Multiple studies have been performed both in vitro and in vivo, characterizing the mechanisms through which EPO exerts its neurotrophic action. In some cases, clinical trials involving EPO have been performed, highlighting its therapeutic potential. Together, all these works indicate the potential beneficial effects of EPO.

scholarly journals Neural Stem Cell-Conditioned Medium Suppresses Inflammation and Promotes Spinal Cord Injury Recovery

2017 ◽  
Vol 26 (3) ◽  
pp. 469-482 ◽  
Author(s):  
Zhijian Cheng ◽  
Dale B. Bosco ◽  
Li Sun ◽  
Xiaoming Chen ◽  
Yunsheng Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Conditioned Medium ◽  
Neural Stem Cell ◽  
Therapeutic Potential ◽  
Secondary Injury ◽  
Cord Injury

Spinal cord injury (SCI) causes functional impairment as a result of the initial injury followed by secondary injury mechanism. SCI provokes an inflammatory response that causes secondary tissue damage and neurodegeneration. While the use of neural stem cell (NSC) engraftment to mitigate secondary injury has been of interest to many researchers, it still faces several limitations. As such, we investigated if NSC-conditioned medium (NSC-M) possesses therapeutic potential for the treatment of SCI. It has been proposed that many of the beneficial effects attributed to stem cell therapies are due to secreted factors. Utilizing primary cell culture and murine models of SCI, we determined that systemic treatment with NSC-M was able to significantly improve motor function and lesion healing. In addition, NSC-M demonstrated significant anti-inflammatory potential in vitro and in vivo, reducing inflammatory cytokine expression in both activated macrophages and injured spinal cord tissues. NSC-M was also able to reduce the expression of inducible nitric oxide synthase (iNOS) within the spleen of injured animals, indicating an ability to reduce systemic inflammation. Thus, we believe that NSC-M offers a possible alternative to direct stem cell engraftment for the treatment of SCI.

scholarly journals Rifaximina nel trattamento della malattia diverticolare: potenziale terapeutico ed economico

2005 ◽  
Vol 6 (1) ◽  
pp. 5-20 ◽  
Author(s):  
Orietta Zaniolo ◽  
Mario Eandi
Keyword(s):  
Diverticular Disease ◽  
Bacterial Resistance ◽  
Therapeutic Potential ◽  
National Health System ◽  
Bacterial Overgrowth ◽  
Gas Production ◽  
Bacterial Degradation ◽  
Common Disease ◽  
Disease Symptoms

Antibiotics are commonly used to treat major inflammatory complications of diverticular disease, but apparently there is no rationale for the use of antibiotic therapy in uncomplicated disease, where an inflammatory component is by definition excluded. Some observations suggest a possible role of gut microflora in determining some symptoms related to diverticular disease: bacterial overgrowth, amplifying gas production and bacterial degradation of fibres, could determine bloating, pain and high fecal density. Therefore a beneficial antibiotic action on diverticular disease symptoms can be hypothesized. In this paper pharmacokinetic, pharmacodinamic and therapeutic potential of an intestinal antibiotic, rifaximin, are reviewed. Rifaximin is a rifamycin derivative which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. It is virtually unabsorbed after oral administration and in vitro data indicate it to possess a broad spectrum of action; bacterial resistance during exposure to rifaximin has been reported but its clinical importance remains to be fully defined. The results of placebo-controlled clinical trials show that cyclic administration of rifaximin is more effective in reducing symptoms and in preventing complications than fibre supplementation alone; the drug appears to be well tolerated and safe. We consider the clinical implications and economical impact of diverticulosis on the Italian National Health System and the patient, with a particular attention on the cost of hospitalization, surgery and global management of diverticulitis and other common disease complications. The hypothetic savings correlated to the reduction of complications incidence, attainable with rifaximin use have been calculated and the comparison between the different acquisition costs of the drug frequently used to treat the diverticular disease is provided. Finally we reviewed some quality of life trials in which the psychological and sociological influence of the disease symptoms and treatments on the patient are assessed.

Broadly Neutralizing Antibodies for HIV Prevention

2020 ◽  
Vol 71 (1) ◽  
pp. 329-346 ◽  
Author(s):  
Shelly T. Karuna ◽  
Lawrence Corey
Keyword(s):  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Broadly Neutralizing Antibodies ◽  
Efficacy Trials ◽  
Preclinical Trials ◽  
Favorable Safety ◽  
Hiv Envelope ◽  
Near Future

In the last decade, over a dozen potent broadly neutralizing antibodies (bnAbs) to several HIV envelope protein epitopes have been identified, and their in vitro neutralization profiles have been defined. Many have demonstrated prevention efficacy in preclinical trials and favorable safety and pharmacokinetic profiles in early human clinical trials. The first human prevention efficacy trials using 10 sequential, every-two-month administrations of a single anti-HIV bnAb are anticipated to conclude in 2020. Combinations of complementary bnAbs and multi-specific bnAbs exhibit improved breadth and potency over most individual antibodies and are entering advanced clinical development. Genetic engineering of the Fc regions has markedly improved bnAb half-life, increased mucosal tissue concentrations of antibodies (especially in the genital tract), and enhanced immunomodulatory and Fc effector functionality, all of which improve antibodies' preventative and therapeutic potential. Human-derived monoclonal antibodies are likely to enter the realm of primary care prevention and therapy for viral infections in the near future.

scholarly journals Therapeutic Potential of Niche-Specific Mesenchymal Stromal Cells for Spinal Cord Injury Repair

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 901
Author(s):  
Susan L. Lindsay ◽  
Susan C. Barnett
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stromal Cells ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Biological Properties ◽  
Cord Injury

The use of mesenchymal stem/stromal cells (MSCs) for transplant-mediated repair represents an important and promising therapeutic strategy after spinal cord injury (SCI). The appeal of MSCs has been fuelled by their ease of isolation, immunosuppressive properties, and low immunogenicity, alongside the large variety of available tissue sources. However, despite reported similarities in vitro, MSCs sourced from distinct tissues may not have comparable biological properties in vivo. There is accumulating evidence that stemness, plasticity, immunogenicity, and adaptability of stem cells is largely controlled by tissue niche. The extrinsic impact of cellular niche for MSC repair potential is therefore important, not least because of its impact on ex vivo expansion for therapeutic purposes. It is likely certain niche-targeted MSCs are more suited for SCI transplant-mediated repair due to their intrinsic capabilities, such as inherent neurogenic properties. In addition, the various MSC anatomical locations means that differences in harvest and culture procedures can make cross-comparison of pre-clinical data difficult. Since a clinical grade MSC product is inextricably linked with its manufacture, it is imperative that cells can be made relatively easily using appropriate materials. We discuss these issues and highlight the importance of identifying the appropriate niche-specific MSC type for SCI repair.

Chemokines in Respiratory Viral Infections: Focus on Their Diagnostic and Therapeutic Potential

2011 ◽  
Vol 31 (4) ◽  
pp. 341-356 ◽  
Author(s):  
Virginia Amanatidou ◽  
Apostolos Zaravinos ◽  
Stavros Apostolakis ◽  
Demetrios A. Spandidos
Keyword(s):  
Viral Infections ◽  
Therapeutic Potential ◽  
Respiratory Viral Infections
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