• Vero E6
• cellular uptake
• enhancing cellular uptake
• ivermectin
• liposomes

• Liposomes/chemistry
• Ivermectin/administration & dosage
• Ivermectin/chemistry
• Ivermectin/pharmacokinetics
• Animals
• Antiparasitic Agents/administration & dosage
• Antiparasitic Agents/chemistry
• Chlorocebus aethiops
• Vero Cells
• Particle Size
• Solubility
• Drug Compounding/methods
• Humans
• Drug Carriers/chemistry
• SARS-CoV-2/drug effects
• Biological Availability

• Drosophila melanogaster
• Orius laevigatus
• coumarin-1,2,4-triazole hybrids
• insecticidal activity

• Animals
• Drosophila melanogaster/drug effects
• Triazoles/chemistry
• Triazoles/pharmacology
• Coumarins/chemistry
• Coumarins/pharmacology
• Insecticides/chemistry
• Insecticides/pharmacology
• Structure-Activity Relationship
• Molecular Docking Simulation
• Molecular Structure

• Actinomycetes
• Antibacterial activity
• Nocardiopsis
• Periplaneta fuliginosa
• Phytotoxic activity
• Secondary metabolites

• Biodiversity
• Periplaneta/microbiology
• Actinobacteria/isolation & purification
• Actinobacteria/physiology
• Anti-Bacterial Agents/pharmacology
• Toxins, Biological/toxicity
• Complex Mixtures
• Symbiosis
• Echinochloa/drug effects
• Echinochloa/growth & development
• Secondary Metabolism/drug effects
• Microbial Sensitivity Tests
• Malvaceae/drug effects
• Malvaceae/growth & development

• Animals
• Myiasis/drug therapy
• Sheep
• Sheep Diseases/drug therapy
• Homeopathy/methods
• Ointments/therapeutic use
• Calliphoridae
• Sulfur/pharmacology
• Sulfur/therapeutic use
• Female
• Larva/drug effects
• Diptera/drug effects

• Streptomyces avermitilis
• antiparasitic
• avermectin
• biocide
• macrocyclic lactones

• Agricultural sustainability
• Biopesticides
• Crop protection
• Pathogen
• Pest

• FSCV
• Ivermectin
• Parkinson’s
• Purinergic P2X4 receptors
• Receptors

• R01 AA022448 NIAAA NIH HHS
• R01 AA030577 NIAAA NIH HHS
• R01AA030577 NIAAA NIH HHS
• R01AA022448 NIAAA NIH HHS
• National Institute on Alcohol Abuse and Alcoholism
• Office of Research and Creative Activities, Brigham Young University
• USC Institute of Addiction Science

• Albendazole
• Ivermectin
• Mass drug administration
• Preventive chemotherapy
• Soil-transmitted helminths

• Ivermectin/therapeutic use
• Ivermectin/administration & dosage
• Humans
• Mass Drug Administration
• Helminthiasis/epidemiology
• Helminthiasis/prevention & control
• Helminthiasis/drug therapy
• Soil/parasitology
• Anthelmintics/therapeutic use
• Anthelmintics/administration & dosage
• Endemic Diseases/prevention & control
• Animals
• Prevalence

• National Health and Medical Research Council

• Avermectins
• Morphometry
• Prepubertal period
• Restraint stress
• Testis
• Testosterone

• Humans
• Rats
• Male
• Animals
• Adolescent
• Testis
• Ivermectin/pharmacology
• Testosterone/pharmacology

• Anopheles arabiensis
• Fecundity
• Ivermectin
• Mortality
• Survival rate

• ETH-13/0025 The Norwegian Programme for Capacity Development in Higher Education and Research for Development
• The Norwegian Programme for Capacity Development in Higher Education and Research for Development

• Ivermectin
• Mass drug administration
• Preventive chemotherapy
• Soil-transmitted helminths

• COVID-19
• Pharmacotherapy
• SARS-CoV-2

• Humans
• Antiviral Agents/therapeutic use
• Antiviral Agents/pharmacology
• COVID-19
• SARS-CoV-2
• Antibodies, Viral
• Antibodies, Monoclonal

• Ain Shams University

• CD4+ T cell subsets.
• T cells
• autoimmune diseases
• ivermectin
• multiple sclerosis

• Animals
• Mice
• CD8-Positive T-Lymphocytes/metabolism
• Encephalomyelitis, Autoimmune, Experimental
• Interleukin-17/metabolism
• Interleukin-2/metabolism
• Ivermectin/pharmacology
• Mice, Inbred C57BL
• Multiple Sclerosis/drug therapy
• STAT5 Transcription Factor/metabolism
• T-Lymphocytes, Regulatory
• Th17 Cells

• SYLYC2022138, SYL20060187, and SYL20060189 Postgraduate Cultivating Innovation and Quality Improvement Action Plan of Henan University
• 21A310005 Key Project of Henan Education Committee
• U2004104 National Natural Science Foundation of China

• Centro de Excelencia Severo Ochoa 2019-2023 Spanish Ministry of Science and Innovation
• CERCA program Generalitat de Catalunya

• Amyotrophic Lateral Sclerosis
• Animal models
• Behavior
• C9ORF72
• Danio rerio
• FUS
• Model validity
• SOD1
• TARDBP
• TDP-43
• Zebrafish

• Cluster-randomized
• Endectocides
• Ivermectin
• Malaria
• Mozambique

• Child
• Humans
• Animals
• Cattle
• Ivermectin/therapeutic use
• Mass Drug Administration
• One Health
• Mosquito Control/methods
• Mosquito Vectors
• Malaria/epidemiology
• Insecticides
• Culicidae/parasitology
• Kenya/epidemiology

• BOHEMIA Unitaid

• An. arabiensis
• Ethiopia
• Ivermectin
• Laboratory mosquitoes
• Mosquito mortality
• Wild mosquitoes

• Humans
• Allosteric Regulation
• Analgesics/pharmacology
• Analgesics/therapeutic use
• Binding Sites
• Chronic Pain/drug therapy
• Receptors, Glycine/metabolism
• Spinal Cord Dorsal Horn/metabolism

• COVID-19
• infection control
• public health
• tropical medicine

• Adult
• COVID-19
• Chagas Disease/drug therapy
• Chagas Disease/epidemiology
• Cross-Sectional Studies
• Humans
• Ivermectin/therapeutic use
• Middle Aged
• Pandemics

• GLRA German Leprosy and Tuberculosis Relief Association

The entire globe is reeling under the magnitude of the current corona virus pandemic. This menace has proposed severe health and economic threats for all, thereby challenging our human existence itself. Since its outbreak, it has raised the concern and imperative need of developing novel and effective agents to combat viral diseases and now its variants as well. Despite the sincere and concerted efforts of scientists and pharma giants all over the world, there seems to be no ideal recourse found till date. Natural products are rich sources of novel compounds used in the treatment of infectious and non-infectious diseases. There are reports on natural products from microbes, plants and marine organisms that are active against viral targets. Actinobacteria, the largest phylum under the bacterial kingdom, is known for its secondary metabolite production with diverse bioactive potentials. Nearly 65% of antibiotics used in medicine are contributed by Actinobacteria. Compared to antibacterial and antifungal agents, antiviral compounds from Actinobacteria are less studied. In recent years Actinobacteria from under studied/extreme ecosystems are explored for their antiviral properties. Ivermectin and teicoplanin are examples of Actinobacteria-derived antiviral drugs available for commercial use. This review highlights the importance of actinobacteria as future sources of antiviral drug discovery.

The emergent outbreak of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emphasized the requirement for therapeutic opportunities to overcome this pandemic. Ivermectin is an antiparasitic drug that has shown effectiveness against various agents, including SARS-CoV-2. This study aimed to assess the efficacy of ivermectin treatment compared with the standard of care (SOC) among people with mild to moderate COVID-19 symptoms.

In this randomized, double-blind, placebo-controlled, single-center, parallel-arm, superiority trial among adult hospitalized patients with mild to moderate COVID-19, 72 patients (mean age 48.57 ± 14.80 years) were randomly assigned to either the ivermectin (n=36) or placebo (n=36) group, along with receiving standard care. We aimed to compare the negativity of reverse transcription polymerase chain reaction (RT-PCR) result at days 7 and 14 of enrolment as the primary outcome. The secondary outcomes were duration of hospitalization, frequency of clinical worsening, survival on day 28, and adverse events.

At days 7 and 14, no differences were observed in the proportion of PCR-positive patients (RR 0.97 at day 7 (p=0.759) and 0.95 at day 14 (p=0.813). No significant differences were found between the groups for any of the secondary endpoints, and no adverse events were reported.

No difference was found in the proportion of PCR-positive cases after treatment with ivermectin compared with standard care among patients with mild to moderate COVID-19 symptoms. However, early symptomatic recovery was observed without side effects.

ClinicalTrials.gov NCT05076253. Registered on 8 October 2021, prospectively.

The online version contains supplementary material available at 10.1186/s13063-022-06649-3.

• COVID-19
• Efficacy
• Ivermectin
• RT-PCR
• Randomized controlled trial
• SARS-CoV-2

High cytotoxicity and increasing resistance reports of existing chemotherapeutic agents against T. evansi have raised the demand for novel, potent, and high therapeutic index molecules for the treatment of surra in animals. In this regard, repurposing approach of drug discovery has provided an opportunity to explore the therapeutic potential of existing drugs against new organism. With this objective, the macrocyclic lactone representative, ivermectin, has been investigated for the efficacy against T. evansi in the axenic culture medium. To elucidate the potential target of ivermectin in T. evansi, mRNA expression profile of 13 important drug target genes has been studied at 12, 24, and 48 h interval. In the in vitro growth inhibition assay, ivermectin inhibited T. evansi growth and multiplication significantly (p < 0.001) with IC₅₀ values of 13.82 μM, indicating potent trypanocidal activity. Cytotoxicity assays on equine peripheral blood mononuclear cells (PBMCs) and Vero cell line showed that ivermectin affected the viability of cells with a half-maximal cytotoxic concentration (CC₅₀) at 17.48 and 22.05 μM, respectively. Data generated showed there was significant down-regulation of hexokinase (p < 0.001), ESAG8 (p < 0.001), aurora kinase (p < 0.001), casein kinase 1 (p < 0.001), topoisomerase II (p < 0.001), calcium ATPase 1 (p < 0.001), ribonucleotide reductase I (p < 0.05), and ornithine decarboxylase (p < 0.01). The mRNA expression of oligopeptidase B remains refractory to the exposure of the ivermectin. The arginine kinase 1 and ribonucleotide reductase II showed up-regulation on treatment with ivermectin. The ivermectin was found to affect glycolytic pathways, ATP-dependent calcium ATPase, cellular kinases, and other pathway involved in proliferation and maintenance of internal homeostasis of T. evansi. These data imply that intervention with alternate strategies like nano-formulation, nano-carriers, and nano-delivery or identification of ivermectin homologs with low cytotoxicity and high bioavailability can be explored in the future as an alternate treatment for surra in animals.

• Bifidobacterium
• COVID-19
• SARS-CoV-2
• TNF-α (tumor necrosis factor a)
• ivermectin
• microbiome

• Adverse drug events
• Pharmacovigilance
• SARS-CoV-2
• Therapeutic drug monitoring

The current research has centered on the use of pharmacological and binding affinity methods to test the 36 compounds as bioactive constituents’ inhibitors for COVID-19. Six compounds out of 36 phytoconstituents (rutin, quercetin, catechin gallate, rhamnetin, campesterol and stigmasterol) have demonstrated outstanding molecular docking and drug-like properties as HIV inhibitors Lopinavir and Indinavir. Interestingly, the lowest binding energies (LBE) and the inhibition constant (K_i) have showed that these compounds are able to bind to the P-glycoprotein substrate of 3CL^pro and Nsp15. Interestingly, rutin has been found to be an excellent potential inhibitor for COVID-19 proteins because it has the best LBE score and K_i value than those of other compounds, and of its ability to form strong H-bonds with COVID-19 proteins. The compounds that come next to the rutin compound are stigmasterol and campesterol. As a result, these compounds are considered possible novel inhibitors of COVID-19. In order to validate the computational results, more in vitro and in vivo investigations are required to support the findings of this research.

The outbreak of SARS-CoV-2 pandemic has triggered unprecedented social, economic and health challenges. To control and reduce the infection rate, countries employed non-pharmaceutical measures such as social distancing, isolation, quarantine, and the use of masks, hand and surface sanitisation. Since 2021 a global race for COVID-19 vaccination ensued, mainly due to a lack of equitable vaccine production and distribution. To date, no treatments have been demonstrated to cure COVID-19. The scientific World is now considering the potential use of Ivermectin as a prophylactic and treatment for COVID-19. Against this background, the objective of this study is to review the literature to demystify the enigma or panacea in the use of Ivermectin. This paper intends to investigate literature which supports the existence or shows the nonexistence of a causal link between Ivermectin, COVID-19 mortality and recovery. There are inconsistent results on the effectiveness of Ivermectin in the treatment of COVID-19 patients. Some studies have asserted that in a bid to slow down the transmission of COVID-19, ivermectin can be used to inhibit the in vitro replication of SARS-CoV-2. The pre-existing health system burdens can be alleviated as patients treated prophylactically would reduce hospital admissions and stem the spread of COVID-19. On a global scale, Ivermectin is currently used by about 28% of the world's population, and its adoption is presently about 44% of countries. However, the full administration of this drug would require further tests to establish its clinical effectiveness and efficacy.

• COVID-19
• Ivermectin
• Prophylactic
• SARS-CoV-2

• Drug repurposing
• Ivermectin
• Mechanism of action
• Molecular docking/dynamic simulation
• SARS-CoV-2

Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic concentration of the drug in a clinically critical site of viral pathology. In this study, the pharmacokinetics (PK) and safety of inhaled dry powders of ivermectin with lactose were investigated in healthy mice.

Female BALB/c mice received ivermectin formulation by intratracheal administration at high (3.15 mg/kg) or low doses (2.04 mg/kg). Plasma, bronchoalveolar lavage fluid (BALF), lung, kidney, liver, and spleen were collected at predetermined time points up to 48 h and analyzed for PK. Histological evaluation of lungs was used to examine the safety of the formulation.

Inhalation delivery of ivermectin formulation showed improved pharmacokinetic performance as it avoided protein binding encountered in systemic delivery and maintained a high exposure above the in vitro antiviral concentration in the respiratory tract for at least 24 h. The local toxicity was mild with less than 20% of the lung showing histological damage at 24 h, which resolved to 10% by 48 h.

• COVID-19
• dry powder aerosol
• inhalable ivermectin
• lactose
• pharmacokinetics
• safety
• spray drying

• Avermectin B1a
• Avermectins
• Precursor supply
• Streptomyces avermitilis
• aveC

• P-glycoprotein
• Avermectin
• COVID-19
• ivermectin
• poisoning

• COVID-19
• ICU-admission
• ivermectin
• mortality
• safety

• Adult
• Humans
• Ivermectin/therapeutic use
• SARS-CoV-2
• COVID-19 Drug Treatment

• COVID-19
• Coronavirus disease 2019
• Ivermectin
• SARS-CoV-2

• Antiviral Agents/adverse effects
• Antiviral Agents/pharmacokinetics
• Antiviral Agents/therapeutic use
• Clinical Trials as Topic
• Drug Repositioning
• Humans
• Ivermectin/administration & dosage
• Ivermectin/adverse effects
• Ivermectin/pharmacokinetics
• Ivermectin/therapeutic use
• Pre-Exposure Prophylaxis/methods
• COVID-19 Drug Treatment

• Cytokines
• Immunotoxicity
• Ivermectin
• NF-κB pathway
• Phagocytosis

• Animals
• Ivermectin/toxicity
• Macrophages/metabolism
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Reactive Oxygen Species
• Signal Transduction

Nanomedicine provides innovative strategies that had significantly improved drug and gene delivery and allowed control over the engineering of therapeutics, diagnostics, vaccines, and other medical devices, for a diversity of medical applications. This review focuses on the current attempts to develop potent nanoengineered vaccines and therapeutics against coronaviruses, and the recent fabrication strategies and design principles to control acute infections from the escalating SARS-CoV-2 pandemic. Nanomedical approaches provide versatile platforms that can be utilized to enhance the overall potency, safety, and stability of vaccines, thus augmenting the desired immune response. Their modulable conformational features of size, shape, surface charge, antigen display, and composition allow for precise tuning and optimization of the nanoconstructs for the management of a variety of diseases and pathological conditions. The ability to control the release of their encapsulated cargoes and the possibility of surface decoration with various moieties support the construction of multifunctional nanomaterials that ultimately boost and prolong the immune response elicited and/or therapeutic effects, selectively at the diseased tissues and target sites.

• COVID-19
• Ivermectin
• Renal toxicity
• Vitamin C

• COVID-19
• Ivermectin
• SARS-CoV-2
• Viral load

• COVID-19
• Humans
• Ivermectin
• SARS-CoV-2
• Treatment Outcome
• Viral Load

• Bacteria
• Fungi
• Immunomodulator
• Ionophore
• Parasite
• Virus

Ivermectin is a broad-spectrum antiparasitic medicine, which is often used as a treatment for parasites or as a prophylaxis. While studies have looked at the long-term effects of Ivermectin on helminths, studies have not considered the long-term impacts of this treatment on host health or disease susceptibility. Here, we tracked the effects of early life Ivermectin treatment in Cuban tree frogs (Osteopilus septentrionalis) on growth rates, mortality, metabolically expensive organ size, and susceptibility to Batrachochytrium dendrobatidis (Bd) infection. One year after exposure, there was no effect of Ivermectin exposure on frog mass (X²₁ = 0.904, p = 0.34), but when tracked through the exponential growth phase (~2.5 years) the Ivermectin exposed individuals had lower growth rates and were ultimately smaller (X²₁ = 7.78, p = 0.005; X²₁ = 5.36, p = 0.02, respectively). These results indicate that early life exposure is likely to have unintended impacts on organismal growth and potentially reproductive fitness. Additionally, we exposed frogs to Bd, a pathogenic fungus that has decimated amphibian populations globally, and found early life exposure to Ivermectin decreased disease susceptibility (disease load: X²₁ = 17.57, p = 0.0002) and prevalence (control: 55%; Ivermectin: 22%) over 2 years after exposure. More research is needed to understand the underlying mechanism behind this phenomenon. Given that Ivermectin exposure altered disease susceptibility, proper controls should be implemented when utilizing this drug as an antiparasitic treatment in research studies.

Banana Fusarium wilt disease caused by Fusarium oxyspoum f. sp. cubense (Foc) seriously threatens the banana industry. Foc tropical race 4 (Foc TR4) can infect almost all banana cultivars. Compared with traditional physical and chemical practices, biocontrol strategy using beneficial microbes is considered as an environmentally sound option to manage fungal disease. In this study, a strain, H3-2, isolated from a non-infected banana orchard, exhibited high antifungal activity against Foc TR4. According to its morphological, physiological, and biochemical characteristics, the strain H3-2 was identified as Streptomyces sp. and convinced by the polymorphic phylogenic analysis of 16S rRNA sequences. Extracts of the strain H3-2 suppressed the growth and spore germination of Foc TR4 in vitro by destroying cell membrane integrity and mycelial ultrastructure. Notably, the strain and its extracts showed broad-spectrum antifungal activity against the selected seven fungal phytopathogens. Fourteen chemical compounds in the extracts were identified by gas chromatography–mass spectrometer (GC-MS), primarily phenolic compounds. Additional pot inoculation experiment demonstrated that the fermentation broth of the strain H3-2 promoted the growth of banana seedlings by efficiently inhibiting the spread of banana Fusarium wilt disease. This study demonstrated the potential application of the novel Streptomyces sp. H3-2 for the management of banana Fusarium wilt.

• GC-MS
• Streptomyces sp.
• antifungal mechanism
• banana fusarium wilt
• biocontrol
• pot experiment

• COVID-19
• Convalescent plasma treatment
• cycle threshold (Ct) value
• neutralizing antibody

• Aged
• COVID-19/therapy
• Critical Illness
• Humans
• Immunization, Passive
• Retrospective Studies
• United States
• COVID-19 Serotherapy

• Animal health
• Anthelmintic resistance
• Dirofilaria immitis
• Heartworm disease
• Macrocyclic lactones
• Mechanism of action

• Animals
• Cat Diseases
• Cats
• Dirofilaria immitis
• Dirofilariasis/drug therapy
• Dirofilariasis/epidemiology
• Dirofilariasis/prevention & control
• Dog Diseases/drug therapy
• Dog Diseases/epidemiology
• Dog Diseases/prevention & control
• Dogs
• Lactones