scholarly journals From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?

2021 ◽  
Vol 28 (2) ◽  
Author(s):  
S Rakedzon ◽  
A Neuberger ◽  
A J Domb ◽  
N Petersiel ◽  
E Schwartz
Keyword(s):  
Antiviral Activity ◽  
Clinical Studies ◽  
Antiviral Agents ◽  
Mortality Rates ◽  
In Vivo Studies ◽  
Level Of Evidence ◽  
Substantial Impact ◽  
Clinical Benefits

Abstract Background Nearly a year into the COVID-19 pandemic, we still lack effective anti-SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. Methods We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine (HCQ), mefloquine, artemisinins, ivermectin, nitazoxanide (NTZ), niclosamide, atovaquone and albendazole. Results For HCQ and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of HCQ for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ used either for prevention or treatment of COVID-19. We found two clinical studies of artemisinins and two studies of NTZ for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, HCQ, mefloquine, artemisinins, ivermectin, NTZ and niclosamide, we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. Conclusions As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic or in outbreaks yet to come.

scholarly journals Essential Oils as Treatment Strategy for Alzheimerʼs Disease: Current and Future Perspectives

Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 239-248 ◽  
Author(s):  
Anju Benny ◽  
Jaya Thomas
Keyword(s):  
Essential Oils ◽  
Clinical Studies ◽  
Symptomatic Relief ◽  
Memory Loss ◽  
Clinical Trial Data ◽  
In Vivo Studies ◽  
Scientific Databases ◽  
Preclinical And Clinical Studies

AbstractAlzheimerʼs disease is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Several hypotheses have been put forward to postulate its pathophysiology. Currently, few drugs are available for the management of Alzheimerʼs disease and the treatment provides only symptomatic relief. Our aim is to review the relevant in vitro, in vivo, and clinical studies focused toward the potential uses of essential oils in the treatment of Alzheimerʼs disease. Scientific databases such as PubMed, ScienceDirect, Scopus, and Google Scholar from April 1998 to June 2018 were explored to collect data. We have conducted wide search on various essential oils used in different models of Alzheimerʼs disease. Out of 55 essential oils identified for Alzheimerʼs intervention, 28 have been included in the present review. A short description of in vivo studies of 13 essential oils together with clinical trial data of Salvia officinalis, Salvia lavandulifolia, Melissa officinalis, Lavandula angustifolia, and Rosmarinus officinalis have been highlighted. In vitro studies of remaining essential oils that possess antioxidant and anticholinesterase potential are also mentioned. Our literary survey revealed encouraging results regarding the various essential oils being studied in preclinical and clinical studies of Alzheimerʼs disease with significant effects in modulating the pathology through anti-amyloid, antioxidants, anticholinesterase, and memory-enhancement activity.

scholarly journals Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 777 ◽  
Author(s):  
Javad Sharifi-Rad ◽  
Farzad Kobarfard ◽  
Athar Ata ◽  
Seyed Abdulmajid Ayatollahi ◽  
Nafiseh Khosravi-Dehaghi ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Clinical Studies ◽  
Positive Impact ◽  
Biological Effects ◽  
Food Supplement ◽  
In Vivo Studies ◽  
Plant Chemical ◽  
Food Applications

Members of the Prosopis genus are native to America, Africa and Asia, and have long been used in traditional medicine. The Prosopis species most commonly used for medicinal purposes are P. africana, P. alba, P. cineraria, P. farcta, P. glandulosa, P. juliflora, P. nigra, P. ruscifolia and P. spicigera, which are highly effective in asthma, birth/postpartum pains, callouses, conjunctivitis, diabetes, diarrhea, expectorant, fever, flu, lactation, liver infection, malaria, otitis, pains, pediculosis, rheumatism, scabies, skin inflammations, spasm, stomach ache, bladder and pancreas stone removal. Flour, syrup, and beverages from Prosopis pods have also been potentially used for foods and food supplement formulation in many regions of the world. In addition, various in vitro and in vivo studies have revealed interesting antiplasmodial, antipyretic, anti-inflammatory, antimicrobial, anticancer, antidiabetic and wound healing effects. The phytochemical composition of Prosopis plants, namely their content of C-glycosyl flavones (such as schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin) has been increasingly correlated with the observed biological effects. Thus, given the literature reports, Prosopis plants have positive impact on the human diet and general health. In this sense, the present review provides an in-depth overview of the literature data regarding Prosopis plants’ chemical composition, pharmacological and food applications, covering from pre-clinical data to upcoming clinical studies.

scholarly journals The Comparative Analysis of Antiviral Activity of Native and Modified Fucoidans from Brown Algae Fucus evanescens In Vitro and In Vivo

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 224 ◽  
Author(s):  
Natalya V. Krylova ◽  
Svetlana P. Ermakova ◽  
Vyacheslav F. Lavrov ◽  
Irina A. Leneva ◽  
Galina G. Kompanets ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Brown Algae ◽  
Biological Activities ◽  
Intraperitoneal Administration ◽  
In Vivo Studies ◽  
Mice Model ◽  
Dna And Rna ◽  
Antiviral Activities

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44–56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.

scholarly journals Quercetin as a Novel Therapeutic Approach for Lymphoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Saiedeh Razi Soofiyani ◽  
Kamran Hosseini ◽  
Haleh Forouhandeh ◽  
Tohid Ghasemnejad ◽  
Vahideh Tarhriz ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Hodgkin’S Lymphoma ◽  
Experimental Studies ◽  
Hodgkin's Lymphoma ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Malignant Diseases ◽  
Antitumor Effects

Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.

scholarly journals Inhibition of Filamentation Can Be Used To Treat Disseminated Candidiasis

2006 ◽  
Vol 50 (10) ◽  
pp. 3312-3316 ◽  
Author(s):  
Stephen P. Saville ◽  
Anna L. Lazzell ◽  
Alexander P. Bryant ◽  
Angelika Fretzen ◽  
Alex Monreal ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Developmental Process ◽  
Mortality Rates ◽  
Genetically Engineered ◽  
In Vivo Studies ◽  
Yeast Form ◽  
Active Disease

ABSTRACT Candida albicans remains the leading causative agent of invasive fungal infection. Although the importance of filamentation in C. albicans pathogenesis has been extensively investigated, in vivo studies to date have been unable to dissect the role of this developmental process in the establishment of infection versus the development of active disease as characterized by damage to the host leading to mortality. To address this issue, we genetically engineered a C. albicans tet-NRG1 strain in which filamentation and virulence can be modulated both in vitro and in vivo simply by the presence or absence of doxycycline (DOX): this strain enabled us, in a prior study, to demonstrate that yeast-form cells were able to infect the deep organs but caused no disease unless filamentation (induced by the addition of DOX) was allowed to occur. In the present study, we examined whether inhibiting filamentation (by withdrawing the DOX) at 24 or 48 h postinfection could serve as an effective therapeutic intervention against candidiasis. The results obtained indicate that DOX removal led to an alteration in the morphology of the infecting fungal cells and a dramatic increase in survival, but as with conventional antifungal drug therapy regimens, mortality rates increased markedly the longer this intervention was delayed. These observations reinforce the importance of invasive filamentous growth in causing the damage to the host and the lethality associated with active disease and suggest this process could be fruitfully targeted for the development of new antifungal agents.

Antiviral activities of pyridine fused and pyridine containing heterocycles, a review (From 2000 to 2020)

2021 ◽  
Vol 21 ◽  
Author(s):  
Seyedeh Roya Alizadeh ◽  
Mohammad Ali Ebrahimzadeh
Keyword(s):  
Antiviral Activity ◽  
Biological Activities ◽  
Critical Role ◽  
Antiviral Agents ◽  
Rnase H ◽  
Pyridine Derivatives ◽  
Action Mechanism ◽  
Syncytial Virus

: Heterocyclic compounds play a critical role in medicinal chemistry and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound pyridine showed various applications that acts as an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase of drug resistance, there is an obvious medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display abroad biological activities such as anti-microbial, anti-viral, antioxidant, anti-diabetic, anti-cancer, anti-malaria, analgesic and anti-inflammatory activities, psychopharmacological antagonistic, anti-amoebic agents, and anti-thrombic activity. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories including pyridine containing heterocycles and pyridine fused rings. Structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), Respiratory syncytial virus (RSV), and Cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, Inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarily expressed the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing and is necessary to investigate in vivo and clinical testing for having better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and needs to perform more broad investigations in this field.

scholarly journals The phytochemical composition and in vitro antiviral activity of decoctions from galls of Guiera senegalensis J.F. Gmel. (Combretaceae) and their relative non-toxicity for chickens

2005 ◽  
Vol 72 (2) ◽  
Author(s):  
C.E. Lamien ◽  
A. Meda ◽  
E. Couacy-Hymann ◽  
A.G. Ouedraogo ◽  
O.G. Nacoulma
Keyword(s):  
Antiviral Activity ◽  
In Vivo Studies ◽  
Chemical Parameters ◽  
Skin Cells ◽  
Phytochemical Composition ◽  
A Value ◽  
Daily Dose ◽  
Guiera Senegalensis

Aqueous decoctions obtained from the galls of Guiera senegalensis were screened to determine their phytochemical composition and in vitro antiviral activity against fowlpox virus. In addition, we wanted to investigate the toxic effects, if any, of crude extracts in chickens. Steroids as well as cardiac glycosides not previously reported, an alkaloid, polyphenols and saponins were detected in the various fractions of organic solvents used for extracting the decoctions. Antiviral activity was determined by cytopathic effect inhibition assay in primary chicken embryo skin cells. The 50 % inhibitory concentration (EC50) was shown to be 15.6 µg/ml. Toxicity for cells was established by determining the 50 % cytotoxic concentration (CCy50). A value of 90 µg/ml and a selectivity index (CCy50/EC50) of 5.8 were obtained. In vivo studies of toxicity were performed in chickens that were dosed orally with decoctions of several concentrations for 2 weeks and then monitored for 3 months. No significant changes in several blood chemical parameters were obtained, except for a significant decline in SGOT levels in birds dosed with 100 mg/kg. These levels were nevertheless within the accepted normal range. The findings suggest that aqueous decoctions of galls from G. senegalensis are non-toxic for chickens when administered orally, even at a daily dose of 100 mg/kg for 14 days.

scholarly journals Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2

2021 ◽  
Author(s):  
Kunlakanya Jitobaom ◽  
Chompunuch Boonarkart ◽  
Suwimon Manopwisedjaroen ◽  
Nuntaya Punyadee ◽  
Suparerk Borwornpinyo ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Synergistic Effects ◽  
Active Form ◽  
Cell Types ◽  
Vero Cells ◽  
Clear Cut ◽  
Clinical Benefits ◽  
Repurposed Drugs

Abstract Despite the urgent need for effective antivirals against SARS-CoV-2 to mitigate the catastrophic impact of the COVID-19 pandemic, there are still no proven effective and widely available antivirals for COVID-19 treatment. Favipiravir and Ivermectin are among common repurposed drugs, which have been provisionally used in some countries. There have been clinical trials with mixed results, and therefore, it is still inconclusive whether they are effective or should be dismissed. It is plausible that the lack of clear-cut clinical benefits was due to the finding of only marginal levels of in vivo antiviral activity. An obvious way to improve the activity of antivirals is to use them in synergistic combinations. Here we show that Favipiravir and Ivermectin had the synergistic effects against SARS-CoV-2 in Vero cells. The combination may provide better efficacy in COVID-19 treatment. In addition, we found that Favipiravir had an additive effect with Niclosamide, another repurposed anti-parasitic drug with anti-SARS-CoV-2 activity. However, the anti-SARS-CoV-2 activity of Favipiravir was drastically reduced when tested in Calu-3 cells. This suggested that this cell type might not be able to metabolize Favipiravir into its active form, and that this deficiency in some cell types may affect in vivo efficacy of this drug.

scholarly journals Nitazoxanide and JIB-04 have broad-spectrum antiviral activity and inhibit SARS-CoV-2 replication in cell culture and coronavirus pathogenesis in a pig model

2020 ◽  
Author(s):  
Juhee Son ◽  
Shimeng Huang ◽  
Qiru Zeng ◽  
Traci L. Bricker ◽  
James Brett Case ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Body Weight Gain ◽  
Antiviral Agents ◽  
Cell Types ◽  
Respiratory Syndrome Virus ◽  
Transmissible Gastroenteritis Virus ◽  
Global Public Health ◽  
Dna And Rna

AbstractPathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Two compounds, nitazoxanide and JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50 of 4.90 μM and 0.69 μM, respectively, with specificity indices of greater than 150. Both inhibitors had in vitro antiviral activity in multiple cell types against some DNA and RNA viruses, including porcine transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved body weight gain and survival. These results highlight the potential utility of nitazoxanide and JIB-04 as antiviral agents against SARS-CoV-2 and other viral pathogens.

scholarly journals The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1012
Author(s):  
Carola Mauri ◽  
Alberto Enrico Maraolo ◽  
Stefano Di Bella ◽  
Francesco Luzzaro ◽  
Luigi Principe
Keyword(s):  
Systematic Review ◽  
Bloodstream Infections ◽  
Mortality Rates ◽  
In Vivo Studies ◽  
High Antimicrobial Activity ◽  
Lactam Antibiotic ◽  
Vitro Data ◽  
In Vitro Data

Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing Enterobacterales, 85% of Stenotrophomonas and 6% of MBL-producing Pseudomonas. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially Enterobacterales, much less for Pseudomonas) while waiting for new antimicrobials.

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