Bioorganičeskaâ himiâ

Despite the fact that most of the bacterial genome encodes certain protein molecules, with the development of transcriptomic technologies, many genes have been discovered that transcribe RNA which is not translated into proteins. Such RNAs are called non-coding RNAs (ncRNAs). The study of only a small number of them shows that ncRNAs often act as regulatory molecules in various cellular processes: maintenance of cell wall homeostasis, protection against pathogens, virulence, etc. A special place among them is occupied by the so-called small ncRNAs with a length of ~50–300 nucleotide residues. In most cases, they form duplexes with the mRNA of certain genes, which affects the expression of the latter. However, some ncRNAs are able to directly bind to the target protein. Similar mechanisms of action of small ncRNAs give them some advantages in regulating various cellular processes compared to protein regulatory molecules. For example, when responding to an external or internal signal through small ncRNAs, the cell will need to spend less time and resources due to the absence of the translation stage. Moreover, some ncRNAs have no complete complementarity to their target RNAs, which makes the regulation more flexible, as it allows ncRNAs to participate in the response simultaneously to various cellular signals. In this review, we considered the general mechanisms by which various small ncRNAs allow bacteria to adapt to certain stressful conditions, as well as specific examples of their action in various prokaryotic organisms.

The Herpes simplex virus (HSV) causes a wide range of diseases, ranging from relatively mild primary skin lesions to severe and often fatal episodes of encephalitis. Currently, the most effective drugs for HSV-infected people are nucleoside analogs (e.g., acyclovir) targeting enzymes encoded by viral DNA. The effectiveness of nucleoside analogs is reduced because of poor solubility in water, rapid intracellular catabolism, high cellular toxicity, and the appearance of resistant viral strains. Antisense technology that exploits nucleic acid fragments (NA-based agents) is a promising alternative to antiviral therapy due to the high affinity of these agents to target nucleic acids, their high solubility in water, and lower cellular toxicity. In the last decade, antisense oligonucleotides have been investigated as potential drugs for various diseases associated with “harmful” nucleic acids. Oligonucleotides with different chemical modifications targeted at specific regions of the HSV genome have shown effectiveness in suppressing the virus. siRNA-based agents have demonstrated prolonged and effective (up to 99%) inhibition of HSV replication. Based on the publications reviewed in the review over the past 30 years, it can be concluded about the prospects of using NA-based agents to combat herpes viral infections.

Consumption, white plague, tuberculosis… Only relatively recently, this disease has ceased to be an absolutely death sentence for infected people, but problems of the spread and diagnosis of the disease are still relevant. This paper presents results of the development of a new loop isothermal amplification (LAMP) assay, named TB-ISATEST, which targeting the species-specific gene rv2341 for the differentiation of Mycobacterium tuberculosis from non-tuberculosis mycobacteria. The assay is applicable for quantitative analysis of genomic DNA and allows detecting tenfold difference in concentration. The results of amplification optimization using a unique two-stage protocol based on the method of orthogonal Taguchi matrices are presented for the first time. A theoretical interpretation of the high amplification efficiency values observed in the LAMP reaction is proposed. Limit of detection of the developed assay is 40 copies of genomic DNA per reaction and amplification requires 15 min. In terms of the combination of characteristics, the TB-ISATEST assay surpasses all the known ways for identifying M. tuberculosis by the LAMP method.

A method for manufacturing biochips by photolithography with hydrogel cells made of brush copolymers based on acrylic acid and acrylamide, fixed at one end on the surface of a polymer substrate has been developed. Hydrogel cells with reactive carboxyl groups were used for covalent immobilization of oligonucleotide probes. The effectiveness of the method was demonstrated in the hybridization analysis of DNA by targets of different lengths of the sequence site 7 of the exon of the human ABO gene.

Coronavirus disease 2019 (COVID-19) is a new global pandemic with high morbidity and mortality caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). N-Hydroxycytidine derivatives show promise for combating viral diseases, and in particular, molnupiravir has recently been approved for emergency prophylaxis in the early stages after infection with SARS-CoV-2. Here, a scheme for the synthesis of 5‑halo-2'-azido-substituted derivatives of cytidine and N-hydroxycytidine is proposed. The synthesized compounds were tested on a panel of six RNA viruses, including SARS-CoV-2, enteroviruses, CHIKV, and HIV-1. A number of compounds were able to inhibit the reproduction of SARS-CoV-2 and CHIKV viruses in the micromolar range without noticeable cytotoxicity. The structures of the leader compounds can be used as a starting point for further design of antiviral agents.