For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were
proposed as potential inhibitors of the SARS-CoV-2 main viral protease
(3-chymotrypsin-like, 3CLpro). Based on the created pharmacophore model of the active
site of the protease, a group of compounds were modeled and tested for activity against
3CLpro. The 3CLpro activity was measured using the fluorogenic substrate
Dabcyl-VNSTLQSGLRK(FAM)MA; the efficiency of the proposed approach was confirmed by
comparison with literature data for ebselen and disulfiram. The results of the
experiments performed with bispidine compounds showed that 14 compounds exhibited
activity in the concentration range 1–10 μM, and 3 samples exhibited
submicromolar activity. The structure–activity relationship studies showed that
the molecules containing a carbonyl group in the ninth position of the bicycle exhibited
the maximum activity. Based on the experimental and theoretical results obtained,
further directions for the development of this topic were proposed.
In order to test the antiviral activity, a series of usnic acid derivatives were synthesized, including new, previously undescribed compounds. The activity of the derivatives against three strains of SARS-CoV-2 virus was studied. To understand the mechanism of antiviral action, the inhibitory activity of the main protease of SARS-CoV-2 virus was studied using the developed model as well as the antiviral activity against the pseudoviral system with glycoprotein S of SARS-CoV-2 virus on its surface. It was shown that usnic acid exhibits activity against three strains of SARS-CoV-2 virus: Wuhan, Delta, and Omicron. Compounds 10 and 13 also showed high activity against the three strains. The performed biological studies and molecular modeling allowed us to assume that the derivatives of usnic acid bind in the N-terminal domain of the surface glycoprotein S at the binding site of the hemoglobin decay metabolite.
The effect of UV radiation on plants provokes oxidative stress, accompanied by the production of reactive oxygen species that can have a direct destructive effect on cellular structures and initiate free radical oxidation of proteins, lipids, and nucleic acids. There is an antioxidant defense system in plant cells that includes a complex of low and high molecular weight compounds. Antioxidants with high molecular weight are enzymes, the key of which is peroxidase [PO]. The paper studies changes in PO activity in soft spring wheat seedlings due to grain treatment with small and medium doses of short-wave UV radiation. A UV-dosed irradiation system (Bio-Link Vilber) with the exposure time 0–60 minutes in increments of 10 minutes was used for seed treatment. Pre-soaked wheat seeds were germinated in Petri dishes. PO activity was determined colorimetrically in three-day-old wheat seedlings, according to A. L. Boyarkin [3]. When the source was irradiated for up to 30 minutes, a clear dependence of the PO activity on the exposure time was not established. The maximum increase in peroxidase activity (by 25.9% relative to the control) was detected with 30-minute UV irradiation. A further increase in exposure time led to a significant decrease in enzyme activity. Moreover, vital feedback was revealed between the activity and exposure time in the range of 30–60 minutes.
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