Institute of
bioorganic chemistry

Phage φ29 and related bacteriophages are currently the smallest known tailed viruses infecting various representatives of both Gram-positive and Gram-negative bacteria. Searches conducted using public genomic databases revealed in excess of 2000 sequences that share the characteristic features of phage φ29. An analysis of major capsid proteins (MCPs) of φ29-related phages indicated the dissimilarity of MCP sequences to those of almost all other known Caudoviricetes groups and a possible distant relationship to MCPs of T7-like phages. Sequence searches conducted using HMM revealed the relatedness between φ29-like phages and an unusual lactococcal phage, KSY1 (Chopinvirus KSY1), whose genome contains two genes of RNA polymerase. The combination of the unique features and distinctive origin of φ29-related phages suggests the categorisation of this vast group in a new order or as a new taxon of a higher rank. The results are published in the International Journal of Molecular Sciences. Learn more

Identifying high-affinity antibodies in human blood serum is a non-trivial task due to the extremely small number of circulating B-cells with the specified specificity. A team of scientists from the IBCh RAS proposed an effective approach that allows for the identification of high-affinity antibodies against pathogen proteins while simultaneously mapping epitopes, even in the absence of information about the structure of the pathogen's immunogens. To screen therapeutic antibodies in the blood of recovered donors, only the pathogen's transcriptome is needed to create a polypeptide library of antigens displayed on the surface of a bacteriophage. The work was published in the journal Communications Biology. Learn more

Scientists from the departments of biotechnology and structural biology (IBCH RAS) and Institute of the Chemistry of Plant Substances (Uzbekistan), and D. I. Ivanovsky Institute of Virology synthesized a series of substituted 1,2,4-triazole-3-thione nucleoside analogs and tested their antiviral activity against herpes simplex virus. 1,2,4-Triazole derivatives have a wide range of biological activities and finding new nucleosides based on it is a topical task. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. For ribosides and deoxyribosides produced by enzymatic synthesis, it has been shown that the addition of carbohydrates to mono- and di-substituted 1,2,4-triazole-3-thiols occurs at different nitrogen atoms. All synthesised nucleosides and heterocyclic bases were tested for cytotoxicity and activity against herpes simplex virus 1. Compared to the antiviral drug ribavirin, the selectivity index for the two nucleosides was significantly higher. It was also found that as the lipophilicity of the compounds studied increased, both their activity and toxicity increased. The results are published in the Biomolecules (IF 4.8). Learn more

The papain-like protease PLpro plays a key role in the life cycle of the coronavirus SARS-CoV-2, making this enzyme a promising target for antiviral therapy. In this work a genetically encoded fluorescent sensor for PLpro activity was created. A distinctive feature of the sensor is its design closely mimicking the natural target of PLpro. A high-contrast translocation response (14-fold change in the signal ratio in the nucleus and cytoplasm) makes it possible to reliably detect PLpro activity in human cell cultures not only in the recombinant protease overexpression model, but also during infection with the SARS-CoV-2 virus, as a team of scientists from the Laboratory of genetically encoded molecular tools of IBCH RAS has shown in collaboration with Institute of Molecular Biology of the Russian Academy of Sciences and the Gamaleya Center for Epidemiology and Microbiology. The results are published in the International Journal of Molecular Sciences.

TRPV ion channels realize a huge variety of functions in the human body participating in the temperature and pain sensation, cell division, calcium uptake. Researchers from IBCh RAS and Columbia University analyzed the structure of the key TRPV domain – the ion conducting pore. Using the original “dynamic molecular portrait” approach, they identified three major states of the pore that are common for all TRPVs, called α-closed, π-closed, and π-open. It was shown that the α-closed state is the most hydrophobic and always nonconducting. While the π-closed one is less stable and can easily transit to the open state, which has favorable hydrophobic properties for the ion conduction. The results were published in Communications Chemistry. Learn more