Showing papers by "Anna A. Shtro published in 2022"

Resurgence of Influenza Circulation in the Russian Federation during the Delta and Omicron COVID-19 Era

Abstract: Influenza circulation was substantially reduced after March 2020 in the European region and globally due to the wide introduction of non-pharmaceutical interventions (NPIs) against COVID-19. The virus, however, has been actively circulating in natural reservoirs. In summer 2021, NPIs were loosened in Russia, and influenza activity resumed shortly thereafter. Here, we summarize the epidemiological and virological data on the influenza epidemic in Russia in 2021–2022 obtained by the two National Influenza Centers. We demonstrate that the commonly used baseline for acute respiratory infection (ARI) is no longer sufficiently sensitive and BL for ILI incidence was more specific for early recognition of the epidemic. We also present the results of PCR detection of influenza, SARS-CoV-2 and other respiratory viruses as well as antigenic and genetic analysis of influenza viruses. Influenza A(H3N2) prevailed this season with influenza B being detected at low levels at the end of the epidemic. The majority of A(H3N2) viruses were antigenically and genetically homogenous and belonged to the clade 3C.2a1b.2a.2 of the vaccine strain A/Darwin/9/2021 for the season 2022–2023. All influenza B viruses belonged to the Victoria lineage and were similar to the influenza B/Austria/1359417/2021 virus. No influenza A(H1N1)pdm09 and influenza B/Yamagata lineage was isolated last season.

Discovery of N-Containing (-)-Borneol Esters as Respiratory Syncytial Virus Fusion Inhibitors

Abstract: Respiratory syncytial virus (RSV) causes acute respiratory infections, thus, posing a serious threat to the health of infants, children, and elderly people. In this study, we have discovered a series of potent RSV entry inhibitors with the (-)-borneol scaffold. The active compounds 3b, 5a, 5c, 7b, 9c, 10b, 10c, and 14b were found to exhibit activity against RSV A strain A2 in HEp-2 cells. The most active substances, 3b (IC50 = 8.9 μM, SI = 111) and 5a (IC50 = 5.0 μM, SI = 83), displayed more potency than the known antiviral agent Ribavirin (IC50 = 80.0 μM, SI = 50). Time-of-addition assay and temperature shift studies demonstrated that compounds 3b, 5a, and 6b inhibited RSV entry, probably by interacting with the viral F protein that mediated membrane fusion, while they neither bound to G protein nor inhibited RSV attachment to the target cells. Appling procedures of molecular modeling and molecular dynamics, the binding mode of compounds 3b and 5a was proposed. Taken together, the results of this study suggest (-)-borneol esters to be promising lead compounds for developing new anti-RSV agents.

Toward a Home Test for COVID‐19 Diagnosis: DNA Machine for Amplification‐Free SARS‐CoV‐2 Detection in Clinical Samples

Abstract: Nucleic acid‐based detection of RNA viruses requires an annealing procedure to obtain RNA/probe or RNA/primer complexes for unwinding stable structures of folded viral RNA. In this study, we designed a protein‐enzyme‐free nano‐construction, named four‐armed DNA machine (4DNM), that requires neither an amplification stage nor a high‐temperature annealing step for SARS‐CoV‐2 detection. It uses a binary deoxyribozyme (BiDz) sensor incorporated in a DNA nanostructure equipped with a total of four RNA‐binding arms. Additional arms were found to improve the limit of detection at least 10‐fold. The sensor distinguished SARS‐CoV‐2 from other respiratory viruses and correctly identified five positive and six negative clinical samples verified by quantitative polymerase chain reaction (RT‐qPCR). The strategy reported here can be used for the detection of long natural RNA and can become a basis for a point‐of‐care or home diagnostic test.

Protein and Peptide Substances in the Treatment of Respiratory Syncytial Infection: Current State

Abstract: Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year old and the elderly. Despite its epidemiological relevance, only two drugs are registered for clinical use against RSVI: ribavirin (approved in a limited number of countries due to side effects) and palivizumab (Synagis), which is intended only for the prevention, but not the treatment, of infection. Currently, various research groups are searching for new drugs against RSV, with three main areas of research: small molecules, polymeric drugs (proteins and peptides), and plant extracts. This review is devoted to currently developed protein and peptide anti-RSV drugs.

Cationic Perylene Antivirals with Aqueous Solubility for Studies In Vivo

Abstract: Perylene-based compounds are attracting significant attention due to their high broad-spectrum antiviral activity against enveloped viruses. Despite unambiguous results of in vitro studies and high selectivity index, the poor water solubility of these compounds prevented in vivo evaluation of their antiviral properties. In this work, we synthesized a series of compounds with a perylene pharmacophore bearing positively charged substituents to improve the aqueous solubility of this unique type of antivirals. Three types of charged groups were introduced: (1) quaternary morpholinium salts (3a–b); (2) a 2′-O-l-valinyl-uridine hydrochloride residue (8), and (3) a 3-methylbenzothiazolium cation (10). The synthesized compounds were evaluated based both on antiviral properties in vitro (CHIKV, SARS-CoV-2, and IAV) and on solubility in aqueous media. Compound 10 has the greatest aqueous solubility, making it preferable for pre-evaluation by intragastrical administration in a mouse model of lethal influenza pneumonia. The results indicate that the introduction of a positively charged group is a viable strategy for the design of drug candidates with a perylene scaffold for in vivo studies.

Antiviral activity of adamantane derivatives against respiratory syncytial virus

Abstract: BACKGROUND: Respiratory syncytial infection annually affects large segments of the population around the world. Despite the ease of clinical manifestations in most adults, for children under two years of age, this disease is a serious danger, leading to the development of severe bronchiolitis, even death. AIM: The aim of this study was to search for drugs with antiviral activity among adamantane derivatives. MATERIALS AND METHODS: Preparations of the group of adamantane derivatives were synthesized in the Department of Medicinal Chemistry of Natural Compounds of the N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS. The cytotoxicity and antiviral activity of the compounds were studied in HEp-2 cell culture using the MTT test and enzyme immunoassay, respectively. RESULTS: There were no drugs with high antiviral properties against RSV in this group. CONCLUSIONS: Despite the absence of drugs with pronounced anti-RSV properties, the information obtained in the course of the work can be used for a targeted search for antitumor substances.

Luminescent polyelectrolytes with antiviral activity

Abstract: Radical polymerization was used to synthesize and characterize (co)polymers with sodium styrenesulfonate (NaSS), 4-methacryloylamidosalicylic acid (MASA), and N-vinylpyrrolidone, which have a low cytotoxicity and a high antiviral activity against the human respiratory syncytial virus. The interaction of copolymers with Tb3+ ions was studied. The complexes formed in dilute aqueous solutions at a concentration of MASA units c ⩽ 1 · 10-4 mol L-1 demonstrate a strong luminescence. The luminescence intensity is independent of copolymer composition, but increases when the NaSS units are substituted with uncharged N-vinylpyrrolidone units. The obtained Tb3+ polymer complexes are promising luminescent sensors for the visualization of biological objects interacting with copolymers.