Neurotropic Properties Research Articles

Neurological Involvement with COVID-19 Review

Abstract The available literature on neurological disorders reported in the context of the current COVID-19 pandemic documents an array of manifestations affecting the central nervous system (CNS), the peripheral nervous system (PNS) and muscle. These are based on case reports and small number series mainly from Wuhan, northern Italy and New York. A dearth of knowledge exists in the understanding of whether the neurological manifestations are caused by or merely associations with COVID-19 infection. CNS involvement is observed more commonly, and includes headache, decreased level of consciousness, seizures, encephalopathy and disturbance of smell and taste. The latter has emerged as a prominent often early symptom and is considered an indicator of the neurotropic properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The profound and often times fatal respiratory failure associated with severe COVID-19 possibly has a neurogenic component with involvement of respiratory brainstem nuclei as a result of transneural viral spread from olfactory or bronchopulmonary receptor nerve endings progressing to the medullary respiratory centres. A generalised endotheliitis and prothrombotic inflammatory state leads to cerebrovascular complications with ischaemic strokes (often large vessel), intracerebral haemorrhage and occasionally cerebral venous thrombosis. Acute haemorrhagic necrotising encephalopathy has been described as a neurological manifestation of the cytokine storm. Postinfectious myelitis has been documented. The PNS involvement includes cases of Guillain–Barré syndrome and some of its variants or formes frustes; myositis of varying degree and severity is encountered. Direct viral neurotropic disorders need to be distinguished from secondary neurological disease resulting from systemic multi-organ illness and from mere coincidental co-occurrence of COVID-19 and a neurological condition. Future clinicopathological studies will need to clarify some of these questions.

Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties

Recombinant adeno-associated viruses (rAAVs) are currently considered the safest and most reliable gene delivery vehicles for human gene therapy. Three serotype capsids, AAV1, AAV2, and AAV9, have been approved for commercial use in patients, but they may not be suitable for all therapeutic contexts. Here, we describe a novel capsid identified in a human clinical sample by high-throughput, long-read sequencing. The capsid, which we have named AAVv66, shares high sequence similarity with AAV2. We demonstrate that compared to AAV2, AAVv66 exhibits enhanced production yields, virion stability, and CNS transduction. Unique structural properties of AAVv66 visualized by cryo-EM at 2.5-Å resolution, suggest that critical residues at the three-fold protrusion and at the interface of the five-fold axis of symmetry likely contribute to the beneficial characteristics of AAVv66. Our findings underscore the potential of AAVv66 as a gene therapy vector.

Neurological Manifestations of COVID-19 patients: An Updated Review and Observations of COVID Patients in the National Institute of Neurosciences and Hospital, Dhaka, Bangladesh

Involvement of the nervous system after viral infection is common. Certain viruses show neurotropism. Recent outbreak of severe acute respiratory syndrome CoV 2 (SARSCov- 2) virus has also exhibited neurotropic properties with various neurological manifestations. The pathophysiology of their neurotropism is not yet clearly known. The details of pathophysiology, clinical manifestation and management are expected to be explored in the near future. Here we review the Neurological manifestations of COVID-19 and the early experience in the National Institute of Neurosciences and Hospital.
 J Bangladesh Coll Phys Surg 2020; 38(0): 122-132

SARS-CoV-2 infection of the nervous system: A review of the literature on neurological involvement in novel coronavirus disease-(COVID-19).

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is believed to have emerged from an animal source and has been spreading rapidly among humans. Recent evidence shows that SARS-CoV-2 exhibits neurotropic properties and causes neurological diseases. Here, we review the literature on neurological involvement in SARS-CoV-2 infections and the possible mechanisms of invasion of the nervous system by this virus, to provide a summary and critical analysis of the early reporting of neurological involvement in COVID-19. An exhaustive search of scientific articles on neurological involvement in COVID-19 was performed in the Web of Science, Scopus, Medline/PubMed, and several other databases. Nineteen relevant articles that had been published or were in preprint were carefully selected according to the inclusion and exclusion criteria. Based on our research, we found that patients with COVID-19 can present with neurological symptoms that can be broadly divided into central nervous system involvement, such as headache, dizziness, altered mental state, and disorientation, and peripheral nervous system involvement, such as anosmia and hypogeusia. Most of these patients are in the older age group and exhibit comorbidities, especially hypertension, and severe infection. In extreme presentations of COVID-19, some patients exhibit seizures, stroke, flaccid paraparesis, corticospinal weakness, and even coma. Moreover, the neurological manifestations can occur independently of the respiratory system. In conclusion, SARS-CoV-2 infection can cause multiple neurological syndromes in a more complex presentation. Therefore, this review elucidated the involvement of the nervous system in SARS-CoV-2 infection and will hopefully help improve the management of COVID-19.

Does SARS-Cov-2 invade the brain? Translational lessons from animal models.

The current coronavirus disease (COVID‐19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS‐CoV‐2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS‐CoV‐2. One key finding that may unify these pathogens is that all require angiotensin‐converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS‐CoV‐2 binds to cell membranes, binds angiotensin‐converting enzyme 2 with a higher affinity compared with SARS‐CoV. The expression of this receptor in neurons and endothelial cells hints that SARS‐CoV‐2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune‐mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune‐mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID‐19.

Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection

ObjectiveCoronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. MethodsWe included patients hospitalized at the University Hospital of Rome “Tor Vergata”, medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. ResultsWe included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. ConclusionsPatients with SARS-CoV2 infection frequently present with sNS. These symptoms are present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.

Роль кинуренинов в регуляции поведения и процессов памяти у дрозофилы

Metabolites of the kynurenine pathway of tryptophan metabolism (KPTM) or kynurenines, have a number of neuroactive properties. Disturbances of KPTM are observed in various neuropathologies, such as Huntington, Parkinson, and Alzheimer’s diseases, senile dementia, schizophrenia, depressions, etc. Kynurenines are known to impact processes in nervous cells through two mechanisms — modulation of activity of cellular receptors and modulation of oxidation-reduction potential. Kynurenic acid (KYNA) is a nonspecific antagonist of the ionotropic glutamate receptors and an inhibitor of excitotoxicity. 3-hydroxykynurenine (3HOK) inhibits peroxide oxidation of lipids, but in high concentration owing to an oxidizing autodimerization causes hydrogen peroxide hyperproduction that leads to death of nervous cells. It is convenient to investigate molecular mechanisms of kynurenine neuroactivity on simple model objects, such as bee and Drosophila, where mutations of KPTM genes affect the level of kynurenines. There are several reasons why Drosophila mutants make a good choice to study kynurenine neurotropic properties: 1) Insects do not synthesize NAD from 3HOK, hence, no influence of KPTM defects on power metabolism; 2) Insects do not have certain KPTM metabolites, such as quinolinic acid, which potentiates neurotoxic properties of 3HOK; 3) High level of 3HOK as a response to the synthesis of xanthommatin pigment; 4) Simple methodology of genetic, physiological, molecular and biological research. In Drosophila cardinal (cd) mutant, the accumulation of 3HOK causes irregularities in a male courtship song and the development of synaptic pathology in late stages of imago development. Besides, in cd the age-dependent disturbance of medium-term memory in a paradigm of the conditioned courtship suppression is observed. The above allows to consider cd a model of senile dementia in humans. On the contrary, in cinnabar (cn) mutant with the accumulation of KYNA this neuroprotector has a positive impact on memory and sound production. In general, KPTM products have an activating effect on central nervous system and behavioral processes.

The experimental study of psychotropic and neurotropic properties of Acorus calamus leaves

The experimental study of psychotropic and neurotropic properties of Acorus calamus leaves

The effects of interleukin-10 and fibroblasts growth factor-2 in mice with toxic cuprizone model of demyelination

Cytokines and growth factors exhibit neurotropic, anti-inflammatory and immunomodulatory properties, and therefore can affect the functioning of the nervous system at demyelinating disorders.Purpose. To identify changes in T-lymphocytes, macrophages, oxidative stress and antioxidant defence factors, endocrine thymus function in the brain and behaviour of mice receiving neurotoxin cuprizone and recombinant human proteins: interleukin-10 (rhIL-10) and fibroblast growth factor (rhFGF-2).Materials and methods. 4-6-month-old 129/Sv mice received cuprizone with food every day for 3 weeks. From the 7th day of cuprizone diet, they received different doses of rhIL-10 and rhFGF-2. The content of СD3+ Т-cells, macrophages, malondialdehyde, activity of antioxidant enzymes in the brain and the level of thymulin in the blood were determined. Behavioural reactions were assessed in the “open field” test.Results. In the brain of mice receiving cuprizone and rhIL-10, there was a decrease in the number of СD3+ Т-cells and the activity of macrophages, which significantly increased under the influence of the toxin. After cytokine injection, the activity of superoxide dismutase, catalase and glutathione peroxidase increased significantly in the brain, as well as the level of thymulin in the blood. Motor, emotional and exploratory activity of mice, significantly suppressed by the cuprizone, was increased after the introduction of rhIL-10. The effect of rhIL-10 on the test parameters is more pronounced at a dose of 5 μg/kg than 50 μg/kg. After injection of rhFGF-2 in the mice with cuprizone diet, there is a decrease in the activity of brain macrophages and an increase of the level of thymulin in the blood depending on the dose of this factor; the motor activity of these animals increased regardless of the rhFGF-2 dose.Conclusion. The injections of rhIL-10 and rhFGF-2 provide dose-dependent positive effects on the pathogenetic factors of experimental demyelinating pathology, as well as the functional state of the nervous system. Whereas, the injections of rhIL-10 have more pronounced effects.

Advantages of Vasoactive Intestinal Peptide for the Future Treatment of Parkinson’s Disease

Parkinson's disease is the second most common neurodegenerative disorder in adults over the age of 65. The characteristic symptoms of Parkinson's disease, such as resting tremor, muscular rigidity, bradykinesia, postural instability and gait imbalance, are thought to be a result of the progressive degeneration of the dopaminergic neurons of the substantia nigra compacta, resulting in insufficient dopamine integrated signalling on GABAergic medium spiny neurons in the striatum. Despite tremendous research, the molecular mechanisms underlying the pathogenesis of neurodegeneration in Parkinson's disease have remained largely unknown. Although a variety of possible pathogenic mechanisms have been proposed over the years, including excessive release of oxygen free radicals, impairment of mitochondrial function, loss of trophic support, abnormal kinase activity, disruption of calcium homeostasis, dysfunction of protein degradation and neuroinflammation, the pathogenesis is still largely uncertain, and there is currently no effective cure for Parkinson's disease. To develop potential therapies for Parkinson's disease, inflammatory processes, mitochondrial dynamics, oxidative stress, production of reactive aldehydes, excitotoxicity and synucleinopathies are to be targeted. In this respect, vasoactive intestinal peptide has beneficial effects that provide an advantage for the treatment of Parkinson's disease. Vasoactive intestinal peptide is a major neuropeptide-neurotransmitter having antioxidant, anti-inflammatory, neurotropic, neuromodulator, and anti-apoptotic properties. In addition to its direct neuroprotective actions regulating the activity of astrocytes, microglia and brain mast cells, it also plays important roles for neuronal adaptation, maintenance and survival.

Synthesis and Neurotropic Activity of 4-Phenylpyridine-3-Carboxylic Acid and 3-Hydroxy-4-Phenylthieno[2,3-b]-Pyridine Derivatives

Aseries of pyridine-3-carboxylic acid derivatives were synthesized via recyclization of a thiopyran ring using cyclic secondary amines and then converted into substituted thieno[2,3-b]pyridines. Studies of the neurotropic properties identified several synthesized compounds with anticonvulsant activity against corazole-induced seizures. The compounds were active as psychological sedatives and, in contrast with the tranquilizer diazepam, were inactive as central myorelaxants at anticonvulsant doses.

Analysis By Deep Sequencing of Discontinued Neurotropic Yellow Fever Vaccine Strains

Deep sequencing of live-attenuated viral vaccines has focused on vaccines in current use. Here we report characterization of a discontinued live yellow fever (YF) vaccine associated with severe adverse events. The French neurotropic vaccine (FNV) strain of YF virus was derived empirically in 1930 by 260 passages of wild-type French viscerotropic virus (FVV) in mouse brain. The vaccine was administered extensively in French-speaking Africa until discontinuation in 1982, due to high rates of post-vaccination encephalitis in children. Using rare archive strains of FNV, viral RNAs were sequenced and analyzed by massively parallel, in silico methods. Diversity and specific population structures were compared in reference to the wild-type parental strain FVV, and between the vaccine strains themselves. Lower abundance of polymorphism content was observed for FNV strains relative to FVV. Although the vaccines were of lower diversity than FVV, heterogeneity between the vaccines was observed. Reversion to wild-type identity was variably observed in the FNV strains. Specific population structures were recovered from vaccines with neurotropic properties; loss of neurotropism in mice was associated with abundance of wild-type RNA populations. The analysis provides novel sequence evidence that FNV is genetically unstable, and that adaptation of FNV contributed to the neurotropic adverse phenotype.

Neurotropic, Psychoactive, and Analgesic Properties of Benzimidazole and Its Derivatives: Physiological Mechanisms

This review summarizes current data and the results of the authors’ own investigations of the neurotropic, psychoactive, and analgesic properties of benzimidazole and its derivatives. Using a series of compounds of this class as a examples, different aspects of the actions of benzimidazoles on the nervous system of lab animals (mollusks, mice, rats, cats) are considered. The efficacy of benzimidazoles is shown to be due to actions on a number of important physiological mechanisms regulating the functional state of nerve cells and neurotransmitter systems, inflammation processes, and pain.

Synthesis and Neurotropic Activity of New 7-Cyclohexyl-6,7,8,9-Tetrahydro-3H-Pyrazolo[3,4-c]-2,7-Naphthyridine-1,5-Diamines

A method for synthesizing new tricyclic heterocyclic 7-cyclohexyl-6,7,8,9-tetrahydro-3H-pyrazolo- [3,4-c]-2,7-naphthyridine-1,5-diamines from 1,3-dichloro-7-cyclohexyl-5,6, 7,8-tetrahydro-2,7-naphthyridine-4-carbonitrile was elaborated. Investigation of the biological activity of the synthesized compounds showed that several of them exhibited pronounced neurotropic properties.

ПОРІВНЯЛЬНИЙ АНАЛІЗ РЕЗУЛЬТАТІВ IN VIVO СКРИНІНГУ ТА IN SILICO ПРОГНОЗУВАННЯ ПСИХО- ТА НЕЙРОТРОПНИХ ВЛАСТИВОСТЕЙ 3-(N-R,R′-АМІНОМЕТИЛ)-2-МЕТИЛ-1Н-ХІНОЛІН-4-ОНІВ

Мета роботи. Провести аналіз результатів скринінгових in vivo досліджень та ретроспективного in silico прогнозування психо- та нейротропних властивостей 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів за допомогою програми PASS.Матеріали і методи. Аналіз результатів попередніх скринінгових in vivo досліджень психо- та нейротропних властивостей 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів ґрунтувався на опублікованих нами даних. Комп’ютерне прогнозування спектра біологічних властивостей 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів проведено ретроспективно за допомогою системи PASS Online.Результати й обговорення. Систематизація та аналіз результатів проведених раніше експериментальних фармакологічних досліджень показали, що більшість 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів має виразні ноотропні властивості, які у деяких похідних поєднуються з високою антидепресивною активністю, протитривожним ефектом, седативними або, навпаки, стимулювальними властивостями. Аналіз результатів для окремих підгруп 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів дозволив виявити певні зв’язки між хімічною будовою та характером біологічної дії сполук.Результати PASS-прогнозу показали, що найбільш імовірними біологічними ефектами 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів є здатність виступати інгібіторами убіхінол-цитохром с редуктази, глюконат 2-дегідрогенази, пластохінол-пластоціанін редуктази, кінази рецепторів тромбоцитарного фактора росту та енхансерами експресії 3-гідрокси-3-метилглутарил-КоА синтази 2. Показники для ефектів, які хоча б опосередковано можуть впливати на функції ЦНС (активатори потенціалзалежних кальцієвих каналів та інгібітори вивільнення серотоніну), мають значно нижчі значення.Висновки. За умови використання комп’ютерного прогнозування спектра фармакологічної активності 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів за допомогою програми PASS як основного підґрунтя для подальших скринінгових досліджень цей клас сполук було б втрачено як перспективний в аспекті пошуку нових речовин, здатних впливати на функції ЦНС.

Prevalence of IgG Autoantibodies against GD3 Ganglioside in Acute Zika Virus Infection

Zika virus (ZIKV) disease has become a global health emergency with devastating effects on public health. Recent evidences implicate the virus as an emergent neuropathological agent promoting serious pathologies of the human nervous system, that include destructive and malformation consequences such as development of ocular and fetal brain lesions, microcephaly in neonates, and Guillain–Barré syndrome (GBS) in adults. These neurological disorders of both central and peripheral nervous systems are thought to be associated to the neurotropic properties of the virus that has ability to infect neural stem cells as well as peripheral neurons, a hallmark of its pathogenicity. The presence of autoantibodies against gangliosides plays a pivotal role in the etiogenesis of GBS and a variety of neurological disorders. Gangliosides are a class of galactose-containing cerebrosides mainly expressed in nervous system tissues playing a critical role in the physiology of neural cells and neurogenesis. Herein, our findings indicate that patients at acute phase of ZIKV infection without any neurological signs show increased levels of IgG autoantibody against GD3 gangliosides, a class of glycolipid found to be highly expressed in neural stem cell acting in the maintenance of their self-renewal cellular capacity. It is possible that a pathological threshold of these antibodies is only acquired in secondary or subsequent infections. In the light of these evidences, we propose that the target of GD3 by autoimmune responses may possibly has an effect in the neuropathy and neurogenesis disorder seen during ZIKV infection.

Toxic activity and protein identification from the parotoid gland secretion of the common toad Bufo bufo

Anuran toxins released from the skin glands are involved in defence against predators and microorganisms. Secretion from parotoid macroglands of bufonid toads is a rich source of bioactive compounds with the cytotoxic, cardiotoxic and hemolytic activity. Bufadienolides are considered the most toxic components of the toad poison, whereas the protein properties are largely unknown. In the present work, we analysed the cardio-, myo-, and neurotropic activity of extract and the selected proteins from Bufo bufo parotoids in in vitro physiological bioassays carried out on two standard model organisms: beetles and frogs. Our results demonstrate a strong cardioactivity of B. bufo gland extract. The toad poison stimulates (by 16%) the contractility of the insect heart and displays the cardioinhibitory effect on the frog heartbeat frequency (a 27% decrease), coupled with an irreversible cardiac arrest. The gland extract also exhibits significant myotropic properties (a 10% decrease in the muscle contraction force), whereas its neuroactivity remains low (a 4% decrease in the nerve conduction velocity). Among identified peptides present in the B. bufo parotoid extract are serine proteases, muscle creatine kinase, phospholipid hydroperoxide glutathione peroxidase, cytotoxic T-lymphocyte protein, etc. Some proteins contribute to the cardioinhibitory effect. Certain compounds display the paralytic (myo- and neurotropic) properties. As the toad gland extract exhibits a strong cardiotoxic activity, we conclude that the poison is a potent agent capable of slaying a predator. Our results also provide the guides for the use of toad poison-peptides in therapeutics and new drug development.

The psycho- and neurotropic profiling of novel 3-(N-R,R′-aminomethyl)-2-methyl-1H-quinolin-4-ones in vivo

The article presents the study of psycho- and neurotropic properties of novel 3-(N-R,R′-aminomethyl)-2-methyl-1H-quinolin-4-ones in vivo. The research was carried out using the open field test, elevated plus maze, rotarod test, tail suspension test, passive avoidance test after scopolamine-induced amnesia and acute normobaric hypoxia with hypercapnia. As a result, two promising substances have been found. According to our results 3-[[(4-methoxyphenyl)amino]methyl]-2-methyl-1H-quinolin-4-one in the dose of 10 mg/kg shows a specific sedative effect and a considerable anti-amnesic activity. The most interesting N-[(2-methyl-4-oxo-1H-quinolin-3-yl)methyl]-N-phenylbenzamide (100 mg/kg) combines a potent anti-anxiety action, the anti-amnesic activity and a considerable antihypoxic effect. They are of interest for further profound studies as promising psychoactive compounds.

The Content of c-Fos-Positive Neurons in the Cerebral Cortex and Striatum and Behavioral Characteristics in Rats on Cutaneous Application of Antiseptic Dorogov’s Stimulator Paste

Experiments were performed on three groups of male Sprague–Dawley rats, each of six animals. Group 1 consisted of intact animals; group 2 of animals given zinc paste, and group 3 of animals given fraction 3 of antiseptic Dorogov’s stimulator (ASD-3) by application to the skin on the back. Detection of c-Fos-positive neurons in different parts of the brain and studies of behavioral responses demonstrated activation of neurons in the cingulate, motor, and piriform areas of the cerebral cortex and the striatum, with increases in motor and ultrasound activity; there was a correlation between behavioral reactions and activation of neurons in these brain areas. These results provide evidence of the concomitant regulation of behavior by multiple brain structures and that ASD-3 has neurotropic properties.

Evaluation of the physiological activity of venom from the Eurasian water shrew Neomys fodiens

BackgroundAnimal toxins can have medical and therapeutic applications. Principally, toxins produced by insects, arachnids, snakes and frogs have been characterized. Venomous mammals are rare, and their venoms have not been comprehensively investigated. Among shrews, only the venom of Blarina brevicauda has been analysed so far, and blarina toxin has been proven to be its main toxic component. It is assumed that Neomys fodiens employs its venom to hunt larger prey. However, the toxic profile, properties and mode of action of its venom are largely unknown. Therefore, we analysed the cardio-, myo- and neurotropic properties of N. fodiens venom and saliva of non-venomous Sorex araneus (control tests) in vitro in physiological bioassays carried out on two model organisms: beetles and frogs. For the first time, we fractionated N. fodiens venom and S. araneus saliva by performing chromatographic separation. Next, the properties of selected compounds were analysed in cardiotropic bioassays in the Tenebrio molitor heart.ResultsThe venom of N. fodiens caused a high decrease in the conduction velocity of the frog sciatic nerve, as well as a significant decrease in the force of frog calf muscle contraction. We also recorded a significant decrease in the frog heart contractile activity. Most of the selected compounds from N. fodiens venom displayed a positive chronotropic effect on the beetle heart. However, one fraction caused a strong decrease in the T. molitor heart contractile activity coupled with a reversible cardiac arrest. We did not observe any responses of the insect heart and frog organs to the saliva of S. araneus. Preliminary mass spectrometry analysis revealed that calmodulin-like protein, thymosin β-10, hyaluronidase, lysozyme C and phospholipase A2 are present in the venom of N. fodiens, whereas thymosin β4, lysozyme C and β-defensin are present in S. araneus saliva.ConclusionOur results showed that N. fodiens venom has stronger paralytic properties and lower cardioinhibitory activity. Therefore, it is highly probable that N. fodiens might use its venom as a prey immobilizing agent. We also confirmed that S. araneus is not a venomous mammal because its saliva did not exhibit any toxic effects.