Antiparasitic Research Articles

Antiprotozoal Pt(II) Complexes as Luminophores Bearing Monodentate P/As/Sb-Based Donors: An X-ray Diffractometric, Photoluminescence, and 121Sb-Mössbauer Spectroscopic Study with TD-DFT-Guided Interpretation and Predictive Extrapolation toward Bi.

In this study, it is demonstrated that the radiative rate constant of phosphorescent metal complexes can be substantially enhanced using monodentate ancillary ligands containing heavy donor atoms. Thus, the chlorido coligand from a Pt(II) complex bearing a monoanionic tridentate C^N*N luminophore ([PtLCl]) was replaced by triphenylphosphane (PPh3) and its heavier pnictogen congeners (i.e., PnPh3 to yield [PtL(PnPh3)]). Due to the high tridentate-ligand-centered character of the excited states, the P-related radiative rate is rather low while showing a significant boost upon replacement of the P donor by heavier As- and Sb-based units. The syntheses of the three complexes containing PPh3, AsPh3, and SbPh3 were completed by unambiguous characterization of the clean products using exact mass spectrometry, X-ray diffractometry, bidimensional NMR, and 121Sb-Mössbauer spectroscopy (for [PtL(SbPh3)]) as well as steady state and time-resolved photoluminescence spectroscopies. Hence, it was shown that the hybridization defects of the Vth main-group atoms can be overcome by complexation with the Pt center. Notably, the enhancement of the radiative rate constants mediated by heavier coligands was achieved without significantly influencing the character of the excited states. A rationalization of the results was achieved by TD-DFT. Even though the Bi-based homologue was not accessible due to phenylation side reactions, the experimental data allowed a reasonable extrapolation of the structural features whereas the hybridization defects and the excited state properties related to the Bi-species and its phosphorescence rate can be predicted by theory. The three complexes showed an interesting antiprotozoal activity, which was unexpectedly notorious for the P-containing complex. This work could pave the road toward new efficient materials for optoelectronics and novel antiparasitic drugs.

Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy

Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. There is a lack of evidence on the mechanism of pathogenesis and rationales for treatment. We used a female C3H/HeN mouse model that recapitulates key clinical manifestations to study how infection dynamics shape DCD pathology and the impact of treatment with the front-line, anti-parasitic drug benznidazole. Curative treatment 6 weeks post-infection resulted in sustained recovery of gastrointestinal transit function, whereas treatment failure led to infection relapse and gradual return of DCD symptoms. Neuro/immune gene expression patterns shifted from chronic inflammation to a tissue repair profile after cure, accompanied by increased cellular proliferation, glial cell marker expression and recovery of neuronal density in the myenteric plexus. Delaying treatment until 24 weeks post-infection led to partial reversal of DCD, suggesting the accumulation of permanent tissue damage over the course of chronic infection. Our study shows that murine DCD pathogenesis is sustained by chronic T. cruzi infection and is not an inevitable consequence of acute stage denervation. The risk of irreversible enteric neuromuscular tissue damage and dysfunction developing highlights the importance of prompt diagnosis and treatment. These findings support the concept of treating asymptomatic, T. cruzi-infected individuals with benznidazole to prevent DCD development.

Synthesis and in vitro biological activity of chalcone derivatives as potential antiparasitic agents

Kinetoplastids are a group of flagellated protozoans including medically important parasites of the genus Trypanosoma and Leishmania. The corresponding diseases have afflicted humans for centuries. In an effort to combat kinetoplastid infections, a set of 21 chalcones was synthesized and evaluated for their in vitro anti-protozoal efficacy against Trypanosoma brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania infantum. To ensure safety, these compounds underwent a selectivity evaluation by assessing toxicity against a human lung fibroblast cell line. Compound K4 exhibited remarkable and selective trypanocidal activity against T. b. brucei with IC50 value of 0.31 ± 0.27 µM and T. b. rhodesiense with IC50 value of 0.96 ± 0.86 µM. Compound K9 also showed significant trypanocidal activity against T. b. brucei (IC50: 0.45 ± 0.14 µM) and T. b. rhodesiense (IC50: 0.93 ± 0.51 µM). In both compounds, electron withdrawing groups are appended to the styrenyl moiety.

Characterization of the domestic canine and feline population in the city of Mineiros/GO, Brazil

The aim of the present study was to qualitatively and quantitatively characterize the domiciled population of dogs and cats in the city of Mineiros/GO. It is a basic, descriptive quali-quantitative research, through a population survey (animal census type). A total of 20,623 animals were counted, with 16,091 dogs and 4,532 cats. 43% were female dogs, 35.02% male dogs, 12.21% female cats, and 9.77% male cats. 73.89% of the population in this census is characterized as adult and 8.35% as elderly. 84.39% of dogs and cats are not neutered. Only 0.30% of animals have some form of identification (microchip or tattoo). 73.15% of animals were adopted, and 11.02% were born at home. 33.54% have supervised access, and in 27.91% of cases, access is unsupervised. 80.15% received some form of antiparasitic treatment in the last year. 58.57% of animals were vaccinated for rabies. 22.84% have never taken their pets to the veterinarian. The data found provide insights for the development of public policies aimed at controlling zoonoses, urban planning, and animal health in the municipality of Mineiros/GO.

Endoscopic Transventricular Transaqueductal Excision of Fourth Ventricular Neurocysticercosis: 2-Dimensional Endoscopic Video: 2-Dimensional Operative Video.

Ventricular neurocysticercosis is a challenging disease that may cause obstructive hydrocephalus and require surgical intervention.1,2 Cysts of the lateral and third ventricle can be addressed by neuroendoscopy and removal of the cyst, when feasible. Surgical excision of cysts from the fourth ventricle can be achieved through endoscopic or microsurgical techniques, depending on the experience of the surgeon and characteristics of the cyst. Unresectable cysts causing hydrocephalus require cerebrospinal fluid diversion through a ventriculoperitoneal shunt.1-8 Medical therapy consisting of antiparasitic and anti-inflammatory agents should be limited to patients where surgery is a poor option or in cases, where there are residual cysts in the body. Medical therapy can cause an inflammatory response resulting in adherence of the cyst to the ventricular wall, which increases the surgical complication rate. Therefore, surgical cyst excision should always precede medical therapy.2 The endoscopic transventricular transaqueductal approach has been described in the literature as a safe route to resect nonadherent cysts when performed by an experienced neuroendoscopist.1-5 Although descriptions of the procedure exist in the literature, no video outlines its detailed operative steps and relevant anatomy. In this video, we present a case of a 42-year-old woman who presented with obstructive hydrocephalus caused by a third ventricular cestode that migrated into the fourth ventricle during her hospitalization. The patient underwent an endoscopic transventricular transaqueductal excision of a fourth ventricular cyst with complete neurological recovery and without requiring ventricular shunting. The patient consented to the procedure and to the publication of her video and images. Institutional Review Board review is not required for a single case report.

Ivermectin Versus Selamectin and Fipronil as Ectoparasite Treatment in Cats and Dogs: A Literature Review

Ectoparasite is commonly found on the skin and can cause dermatological problems. In veterinary practices, ivermectin, selamectin, and fipronil are commonly used to treat ectoparasitosis. This article aims to deeply examines the indications and contraindications of ivermectin, selamectin and fipronil. Ectoparasites are commonly found in cats and dogs and make up a large percentage of cases compared to other diseases. Therefore, it is important to have an understanding of the drugs that are effective against ectoparasites. In the past, ivermectin was a popular antiparasitic drug due to its high efficacy. However, its safety is not directly proportional its efficacy. Ivermectin has adverse effects, as evidenced by numerous case reports of overdose, intoxication, and interference with certain organ functions. In the field of pharmacology, many new drugs have been developed with the expectation of improved efficacy and safety. Two examples of such drugs are selamectin and fipronil. This article allows veterinarians and other readers to compare the safety and efficacy of these drugs before administering them to their patients.

Harnessing the 12 Green Chemistry Principles for Sustainable Antiparasitic Drugs: Toward the One Health Approach.

Antiparasitic drug development stands as a critical endeavor in combating infectious diseases which, by affecting the well-being of humans, animals, and the environment, pose significant global health challenges. In a scenario where conventional pharmacological interventions have proven inadequate, the One Health approach, which emphasizes interdisciplinary collaboration and holistic solutions, emerges as a vital strategy. By advocating for the integration of One Health principles into the R&D pharmaceutical pipeline, this Perspective promotes green chemistry methodologies to foster the development of environmentally friendly antiparasitic drugs for both human and animal health. Moreover, it highlights the urgent need to address vector-borne parasitic diseases (VBPDs) within the context of One Health-driven sustainable development, underscoring the pivotal role of medicinal chemists in driving transformative change. Aligned with the Sustainable Development Goals (SDGs) and the European Green Deal, this Perspective explores the application of the 12 Principles of Green Chemistry as a systematic framework to guide drug discovery and production efforts in the context of VBPD. Through interdisciplinary collaboration and a constant commitment to sustainability, the field can overcome the challenges posed by VBPD while promoting global and environmental responsibility. Serving as a call to action, scientists are urged to integrate One Health concepts and green chemistry principles into routine drug development practices, thereby paving the way for a more sustainable R&D pharmaceutical pipeline for antiparasitic drugs.

In silico analysis of soybean phytocompounds against Plasmodium falciparum

IntroductionNatural products have been indispensable since immemorial and still act as a supportive healer. Parasitic diseases are a significant hurdle for humans and are responsible for global morbidity and mass mortality. Due to the building up of resistance in parasites over existing drugs and the severe side effects of the drugs, there is an urgent need to explore various plant extracts to discover novel antiparasitic agents. This article deals with the pharmacological aspects of soybeans against Plasmodium falciparum, which causes many of the deadliest and most popular diseases, such as malaria. MethodsThe molecular basis for selective inhibition of soy phytoconstituents like beta-sitosterol, soya-saponin I, soya-saponin II, soya-saponin II methyl ester, dehydrosoyasaponin I, phytic acid, and tryptophyl leucine were evaluated using in silico molecular docking approaches and molecular dynamic simulations against the falcipain-2 (FP2) and phosphoethanolamine methyltransferase (PMT) of P. falciparum. ResultsThe results indicated that tryptophyl leucine exhibited potential inhibitory action against both enzymes based on pharmacophore, molecular docking, simulations, root mean square deviation, root mean square fluctuations, absorption, distribution, metabolism, excretion, and toxicity analyses. ConclusionMedicinal plants represent a treasure for bioactive lead compounds and eventually provide scope for further identification and investigation of novel drug candidates which may be important in the design of selective PfPMT/PfFP-2 inhibitors as potential antimalarials.

A highly selective dual-signal response ratiometric fluorescence sensing strategy for malachite green in fish based on carbon dots/copper nanoclusters nanocomposite

Malachite green (MG), a widely used antiparasitic agent, poses health risks to human due to its genotoxic and carcinogenic properties. Herein, a stable dual-emission fluoroprobe of carbon dots/copper nanoclusters is prepared for highly selective detection of MG based on the inner filter effect. This probe exhibits characteristic emission bands at 435 and 625 nm when excited at 376 nm. After adding MG, the both emission signals were significantly quenched, and the ratio of fluorescence intensity (F435/F625) was linearly related to the concentration of MG in the range of 0.05–40 μmol L−1 with a limit of detection of 18.2 nmol L−1. Meanwhile, the two signals exhibit linear relationships with the concentration of MG, respectively, and the corresponding detection results were consistent. The fluoroprobe was successfully used for the detection of MG in fish samples with the recoveries ranging from 96.0% to 103.8% and a relative standard deviation of <3.3%.

Discovery of 1,3,4-Oxadiazole Derivatives as Broad-Spectrum Antiparasitic Agents.

Vector-borne parasitic diseases (VBPDs) pose a significant threat to public health on a global scale. Collectively, Human African Trypanosomiasis (HAT), Leishmaniasis, and Malaria threaten millions of people, particularly in developing countries. Climate change might alter the transmission and spread of VBPDs, leading to a global burden of these diseases. Thus, novel agents are urgently needed to expand therapeutic options and limit the spread of drug-resistant parasites. Herein, we report the development of broad-spectrum antiparasitic agents by screening a known library of antileishmanial and antimalarial compounds toward Trypanosoma brucei (T. brucei) and identifying a 1,3,4-oxadiazole derivative (19) as anti-T. brucei hit with predicted blood-brain barrier permeability. Subsequently, extensive structure-activity-relationship studies around the lipophilic tail of 19 led to a potent antitrypanosomal and antimalarial compound (27), with moderate potency also toward Leishmania infantum (L. infantum) and Leishmania tropica. In addition, we discovered a pan-active antiparasitic molecule (24), showing low-micromolar IC50s toward T. brucei and Leishmania spp. promastigotes and amastigotes, and nanomolar IC50 against Plasmodium falciparum, together with high selectivity for the parasites over mammalian cells (THP-1). Early ADME-toxicity assays were used to assess the safety profile of the compounds. Overall, we characterized 24 and 27, bearing the 1,3,4-oxadiazole privileged scaffold, as broad-spectrum low-toxicity agents for the treatment of VBPDs. An alkyne-substituted chemical probe (30) was synthesized and will be utilized in proteomics experiments aimed at deconvoluting the mechanism of action in the T. brucei parasite.

Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line.

Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-spectrum activities, IVM is being used excessively in animals which has generated an interest for researchers to investigate its toxic effects. Cytotoxic and genotoxic effects have been reported in animals due to excessive usage of IVM. Therefore, this study aims to evaluate the cytotoxic and genotoxic effects of IVM on the Madin-Darby-Bovine-Kidney (MDBK) cell line by examining the expression of a DNA damage-responsive gene (OGG1). Cytotoxicity of IVM was tested using an assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), whereas the genotoxicity was evaluated using comet assay along with micronucleus assay. Moreover, the gene expression of DNA damage response gene (OGG1) was measured by qRT-PCR, after extraction of RNA from the MDBK cell line using the TRIzol method and its conversion to cDNA by reverse-transcriptase PCR. During the experiment, cell viability percentage was measured at different doses of IVM i.e., 25%, 50%, 75%, along with LC50/2, LC50 and LC50*2. It was observed that the gene expression of OGG1 increased as the concentration of IVM increased. It was concluded that IVM has both cytotoxic and genotoxic effects on the MDBK cell line. Furthermore, it is recommended that studies related to the toxic effects of IVM at molecular level and on other model organisms should be conducted to combat its hazardous effects.

Chemical composition of leaf essential oil of Schinopsis lorentzii and its inhibitory effects against key enzymes relevant to type-2 diabetes: an emphasis on GC-MS chemical profiling and molecular docking studies

Schinopsis lorentzii (Griseb.) Engler is an aromatic plant belonging to Anacardiaceae family, and grown in Argentina, Paraguay, Brazil, and Bolivia. It is a rich source of essential oils and tannins as well as commercially available as vegetable-processed leather tanning and antiparasitic agent. This study was designed to explore the chemical composition of essential oil isolated from S. lorentzii leaves and elaborate on their significance as natural anti-diabetic, combined with molecular-docking studies. The leaf oil was chemically analysed using gas chromatography-mass spectrometry (GC-MS) method and investigated for inhibitory effects against α-amylase and α-glucosidase. Molecular-modelling study via Molecular Operating Environment-Docking (MOE-Dock) program was used to evaluate binding interactions of major components with the above-mentioned targets. The GC-MS analysis of the leaf oil revealed the predominance of β-caryophyllene (21.63±0.36%), γ-terpinene (13.53±0.74%), α-pinene (13.38±0.65%), and terpinen-4-ol (12.55±1.56%). The tested oil expressed a remarkable inhibitory effect against α-amylase with IC50 value of 2.27±0.19 μg/mL, comparable to acarbose (IC50 = 0.52±0.18 μg/mL) used as standard drug. Similarly, it significantly inhibited α-glucosidase (IC50 = 0.84±0.03 μg/mL), compared to acarbose (IC50 = 0.38±0.02μg/mL). The in-silico molecular docking study revealed favorable binding affinities of β-caryophyllene, terpinen-4-ol and sabinene with variable degrees with α-amylase and α-glucosidase. Thus, this study demonstrated valuable scientific data on the leaf oil of S. lorentzii as a potential candidate for the development of natural antidiabetic formulations.

Description of Some Methodologies for the Synthesis of 1,4-Naphthoquinone Derivatives and Examples of their Biological Activity: A Review

Abstract: An alternative to finding new drugs for the treatment of various diseases is the chemical modification of the structure of compounds of natural origin. Among them, naphthoquinones are very interesting candidates, as they are antibacterial, antifungal, antiparasitic, and anticancer agents. Naphthoquinones are redox compounds that can accept one or two electrons, generating reactive oxygen species in the cell and producing cell apoptosis. Naphthoquinones are unsaturated compounds containing a dicarbonyl sequence in the para position, which is highly reactive. Several studies of the chemical modification of naphthoquinones, either of natural origin (such as lapachol or juglone) or synthetic origin, have demonstrated the great importance and versatility of this type of compound. Polyhydroxylated derivatives, amino, thioethers, and conjugated heterosystems (indole or pyrrole groups) have been synthesized. Depending on the type of derivative, their specific use against certain types of microorganisms or cancer cell lines has been demonstrated.

Targeting Cysteine Proteases and their Inhibitors to Combat Trypanosomiasis.

Trypanosomiasis, caused by protozoan parasites of the Trypanosoma genus, remains a significant health burden in several regions of the world. Cysteine proteases play a crucial role in the pathogenesis of Trypanosoma parasites and have emerged as potential therapeutic targets for the development of novel antiparasitic drugs. This review article aims to provide a comprehensive overview of the role of cysteine proteases in trypanosomiasis and their potential as therapeutic targets. We discuss the biological significance of cysteine proteases in Trypanosoma parasites and their involvement in essential processes, such as host immune evasion, cell invasion, and nutrient acquisition. A comprehensive literature search was conducted to identify relevant studies and research articles on the role of cysteine proteases and their inhibitors in trypanosomiasis. The selected studies were critically analyzed to extract key findings and provide a comprehensive overview of the topic. Cysteine proteases, such as cruzipain, TbCatB and TbCatL, have been identified as promising therapeutic targets due to their essential roles in Trypanosoma pathogenesis. Several small molecule inhibitors and peptidomimetics have been developed to target these proteases and have shown promising activity in preclinical studies. Targeting cysteine proteases and their inhibitors holds great potential for the development of novel antiparasitic drugs against trypanosomiasis. The identification of potent and selective cysteine protease inhibitors could significantly contribute to the combat against trypanosomiasis and improve the prospects for the treatment of this neglected tropical disease.

TESTING OF NEW MODERN DRUGS AGAINST ECTOPARASITES OF KARAKUL SHEEP

The article presents pathogens, epizootological data, course and symptoms of sheep psoroptosis. The results of the use of the antiparasitic drug ivermectin - 10 in sheep psoroptosis are also presented. Pathogens, epizootological data, course and symptoms of sheep psoroptosis are given in the article. And also provides the results of the use of an antiparasitic drug - ivermectin - 10 with sheep psoroptosis.

Echinodermata as a Promising Source of Antiparasitic Agents: A Review

Echinodermata as a Promising Source of Antiparasitic Agents: A Review

Nanostructured carrier systems facilitating enhanced delivery of 8-(4-Amino-1 methylbutylamino)-6 methoxyquinoline: a narrative review

8-(4-Amino-1-methylbutylamino)-6-methoxyquinoline, an inhibitor of protozoan growth, presents an opportunity to explore nanostructured drug carriers to overcome these challenges. By encapsulating this compound in nanocarriers such as liposomes, dendrimers or polymeric nanoparticles, you can improve its solubility and protect it from degradation, thereby increasing circulation time and accumulation at the target site. This review will explore various nanostructured carriers for 8-(4-Amino-1-methylbutylamino)-6-methoxyquinoline, analyze their properties, and discuss how nanotechnology can enhance the efficacy of this antiparasitic agent. With the prevalence of parasitic diseases around the globe nanomedicine may provide the solution by enabling more effective delivery of compounds like 8-(4-Amino-1-methylbutylamino)-6-methoxyquinoline.

Human Demodex mites (Acari: Demodicidae) as a possible etiological factor in Rosacea: A cross-sectional study from Turkey

This study was conducted to determine the prevalence and burden of Demodex mites in patients with rosacea, and to investigate their potential contribution to the aetiology of rosacea. The study included 82 patients (44 with papulopustular rosacea and 38 with erythematotelangiectatic rosacea) diagnosed with rosacea by clinical examination and 82 healthy controls without dermatologic disease. Samples were obtained from each participant from the cheek, nasolabial, and chin regions using standardised skin surface biopsy (SSSB). Samples were examined under a light microscope, and Demodex species were identified and counted. Demodex positivity (≥5 mites) was detected in 91% of patients and 20% of controls in the study (p&lt; 0.01). Only D. folliculorum (total 1328, mean 44.27/cm2) was detected in 37% of patients and D. folliculorum + D. brevis coinfection (total 6071, mean 134.91/cm2) in 55% of patients. Only D. folliculorum (total 97, mean 6.06/cm2) was detected in 20% of healthy controls, while D. folliculorum + D. brevis co-infection was not detected. The study showed that Demodex burden in patients with rosacea was approximately 30 times higher than in healthy controls and was caused by coinfection of D. folliculorum and D. brevis (mean Demodex burden: 179.18/cm2 in patients, 6.06/cm2 in healthy controls). It was concluded that Demodex infestation, especially co-infection with D. folliculorum and D. brevis, may be a potential factor in the aetiology of rosacea that should not be ignored in the clinic, and that it may be appropriate to initiate antiparasitic treatment when the parasite is detected.

Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells

Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells. Emetine exhibited potent cytotoxic activity both in hematologic and solid cancer cells and induced AML cell differentiation. Emetine also inhibited AML stem/progenitor cells, as evidenced by decreased expression of CD34, CD97, CD99, and CD123 in KG-1a cells, indicating anti-AML stem/progenitor cell activities. The administration of emetine at a dosage of 10 mg/kg for two weeks showed no significant toxicity and significantly reduced xenograft leukemic growth in vivo. NF-κB activation was reduced in emetine-treated KG-1a cells, as shown by reduced phospho-NF-κB p65 (S529) and nuclear NF-κB p65. DNA fragmentation, YO-PRO-1 staining, mitochondrial depolarization and increased levels of active caspase-3 and cleaved PARP (Asp214) were detected in emetine-treated KG-1a cells. Moreover, treatment with the pancaspase inhibitor Z-VAD(OMe)-FMK partially prevented the apoptotic cell death induced by emetine. Emetine treatment also increased cellular and mitochondrial reactive oxygen species, and emetine-induced apoptosis in KG-1a cells was partially prevented by the antioxidant N-acetylcysteine, indicating that emetine induces apoptosis, at least in part, by inducing oxidative stress. Overall, these studies indicate that emetine is a novel potential anti-AML agent with promising activity against stem/progenitor cells, encouraging the development of further studies aimed at its clinical application.

Enhanced In Vitro Antiviral Activity of Ivermectin-Loaded Nanostructured Lipid Carriers against Porcine Epidemic Diarrhea Virus via Improved Intracellular Delivery.

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of -31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake.