Aim. To study and characterise the features of the course of coronavirus infection in a domestic cat model, as well as to assess the danger of SARSCoV-2 isolated in Russia for these animals based on the data obtained, with the possibility of extrapolating to wild felines.Material and Methods. For the study, model animals – Felis silvestris catus – were divided into 3 groups. The viral strain of SARS-Cov-2/human/RUS/Nsk-FRCFTM-1/2020 was cultivated on Vero E6 cell culture and then administered intranasally in a volume of 200 μl, 105TCID50/ml, to animals from the first and second groups. Model animals from the first group were euthanized and lung fragments were taken on 6–day post infection (d.p.i.), animals from the second group – on 14 d.p.i. The third group – the control group, was injected with saline in an equivalent volume. Histological sections colored with hematoxylin and eosin were investigated for pathomorphological changes in lung tissue using light microscopy.Results. According to the obtained results the pathomorphological picture in the lungs of experimental animals indicates the course of interstitial pneumonia for both 6 and 14 d.p.i. In addition, it has been determined that by 14 d.p.i. the growth of fibrous tissue in the lungs begins to be visualised, indicating the beginning of light regenerative processes.Conclusion. The study showed that cats are susceptible to the SARS-CoV-2 virus, and these model animals are characterized by the emergence of clinical manifestations and morphological patterns in the lungs, which correspond to interstitial pneumonia.

The new coronavirus infection caused by SARS‐CoV‐2 is a dangerous respiratory disease. The aim of the investigation was to study the pathomorphological changes in lungs of Syrian hamsters infected with SARS‐CoV‐2 as is necessary for adequate therapy and prevention of the disease.Syrian hamsters of the SPF category were infected intranasally with a dose of 5×105TCID50 SARS‐CoV‐2/human/RUS/Nsk‐FRCFTM‐1/2020). Animals were euthanised on days 3, 6, 10, 14 and 21 after infection and the lungs were collected. To determine virus replication real‐time RT‐PCR was used. The lungs was used for histological examination. Statistics was performed using Statistics for Windows 10 software.Specific pathological lesions characterising the inflammatory process were detected in all groups of animals. The severity of pathological changes and the volume of lung tissue lesions varied depending on the stage of the disease. The most severe lesions were observed on days 6–10. By day 21, the process of organ structure restoration was noticed.The study showed that pathological changes in the Syrian hamster’s lungs caused by experimental infection with the SARS‐CoV‐2 were multifaceted and complex. In mild cases, congestion and infiltration are observed, and in severe cases, atelectasis and pulmonary edema were life‐threatening. The most severe lesions in lungs were noted on days 6–10. By day 21, the process of restoration was observed.

A large series of new chiral heterocyclic cineol-like methanopyrano[4,3-b]pyrans was prepared by reactions of the (+)- and (–)-isomers of 8-hydroxy-6-hydroxymethyllimonene, obtained from the corresponding α-pinenes with high optical purity, and aromatic aldehydes with OH and/or OMe substituents. The synthesized heterocycles were tested for analgesic activity in the in vivo tests. Some of cineol-like methanopyrano[4,3-b]pyrans synthesized from 4-methoxybenzaldehyde, 2,3,4-trimethoxybenzaldehyde and 2,4,5-trimethoxybenzaldehyde exhibit significant analgesic activity. Experiments in vivo with agonists and antagonists of several neurotransmitter systems helped to elucidate the probable mechanism of analgesic action mediated by these compounds. Thus, cannabinoid CB1 receptors do not appear to be involved in the development of the analgesic effect. Opioid and GABA_A receptors of the central nervous system likely play a significant role in the analgesic activity of the tested cineol-like methanopyrano[4,3-b]pyrans. (3R,4aR,5R,8S,8aS)-5-(4-Methoxyphenyl)-2,2,8a-trimethylhexahydro-2H,5H-3,8-methanopyrano[4,3-b]pyran likely mediates its analgesic effect through both muscarinic and adrenergic receptors of the central nervous system. Serotonin receptors may be involved into the mechanism of analgesic action of (3R,4aR,5R,8S,8aS)-5-(2,3,4-trimethoxyphenyl)-2,2,8a-trimethylhexahydro-2H,5H-3,8-methanopyrano[4,3-b]pyran and (3R,4aR,5R,8S,8aS)-5-(2,4,5-trimethoxyphenyl)-2,2,8a-trimethylhexahydro-2H,5H-3,8-methanopyrano[4,3-b]pyran.

Background. Studying the characteristics of the course of coronavirus infection caused by SARS-CoV-2 remains relevant due to the high mutagenicity of the virus and the prevalence of the disease in the world. The search for new drugs to eliminate clinical manifestations of COVID-19, as well as against its agent, is essential. During the pandemic caused by SARS-CoV-2, dexamethasone was recognized as the only effective anti-inflammatory drug for the treatment of patients with severe form of the disease, but its use leads to a large number of side effects.The aim. To study the therapeutic effect of the drug Molixan in the treatment of coronavirus infection in model animals – Syrian hamsters.Methods. To assess the effectiveness of the drug Molixan, we carried out a visual assessment of the condition of the lungs using light microscopy and the morphometry of the lung tissue of experimentally infected Syrian hamsters on the day 6 after infection under different Molixan treatment regimens and during dexamethasone therapy. The test drug was administered using three different doses (22.2 mg/kg, 44.4 mg/kg and 88.8 mg/kg, which are equivalent to doses of 3 mg/kg, 6 mg/kg and 12 mg/kg of human body weight) once daily or dividing the dose into two within 12 h interval in case of multiple (5 days) intramuscular administration. Dexamethasone (comparison drug) was administered at a dose of 20 mg/kg once daily for 5 days.Results. The studies showed statistically significant effectiveness of using Molixan at a dose of 44.4 mg/kg, divided into two doses, during 5 days. When compared with untreated hamsters, this treatment regimen reduces the degree of generalization and severity of the inflammatory process in the lungs; and the pathomorphological picture is similar to that observed during treatment with Dexamethasone.Conclusion. The studied drug Molixan is effective as an anti-inflammatory drug in the treatment of the disease caused by SARS-CoV-2.

SARS‐CoV‐2: особенности распространения вируса и течение патогенеза коронавирусной инфекции у различных видов животных

Cridanimod (acridoneacetic acid), the active ingredient of the immunomodulatory drug Cycloferon^®, has a well-characterized antiviral profile, but an unexplored analgesic potential. Bornane monoterpenes, notably (+)-camphor and (−)-fenchone, are established scaffolds for analgesic drug design. We therefore synthesized thirteen cridanimod–monoterpene conjugates—seven amides, three acylhydrazones, and three esters—by EDCI/DMAP-mediated coupling or CDI/DBU-promoted esterification, and evaluated them in mice at an oral dose of 10.0 mg/kg in the acetic acid writhing and hot plate tests, with diclofenac sodium (10.0 mg/kg) as the reference. Acridoneacetic acid and Cycloferon^® were themselves inactive in both assays. By contrast, six of the thirteen conjugates were significantly active (p < 0.05) in at least one test, with distinct leads in each: amide 19 matched diclofenac in the writhing test (−63.7% vs. −64.4%), whereas acylhydrazone 23 exceeded diclofenac in the hot plate test (+43.9% vs. +25.7%). The divergent profiles suggest that different structural subclasses engage peripheral and central antinociceptive mechanisms. Conjugation thus converts an analgesically inactive immunomodulator into a substance yielding analgesics that match or exceed a standard NSAID at the same oral dose, providing a promising starting point for the development of new pain-relieving agents.