Press-room / Digest
Natural-Target-Mimicking Translocation-Based Fluorescent Sensor for Detection of SARS-CoV-2 PLpro Protease Activity and Virus Infection in Living Cells
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.
“Molecular portraits” characterized functional states of TRPV ion channels
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
Immune system regulation for nanoparticle drug delivery. Breaking the endless cycle in nanomedicine
The journey of discovery in scientific research sometimes follows a familiar path: discover, admire, investigate, disappoint, and forget. Nevertheless, in some disciplines, it seems repeating many times. One of such cycles in the field of immune system blockade by nanoparticles is analysed in a recent article published in Nature Communications journal. Scientists from the Institute of Bioorganic Chemistry, Uppsala University and Boston University propose that advancements in nanomaterial development may finally disrupt this cycle, potentially introducing the method of macrophage blockade into clinical practice to improve cancer therapy. Learn more
Loss of Ability to regenerate Limbs in Higher Vertebrates: From Side Effects of Evolutionary Innovations to Gene Loss
Researchers from the Laboratory of Molecular Foundations of Embryogenesis at the GNC IBCh RAS have identified the main factors that rendered limb regeneration impossible in modern amniotes (reptiles, birds, and mammals). The authors suggested that after the ancestors of amniotes transitioned to land, their ability to regenerate limbs was suppressed by the side effects of various innovations that emerged at that time, which were necessary for successful colonization of land. This, in turn, stimulated the disappearance of many genes that ceased to participate in regeneration from that moment on. As a result, in modern amniotes, including humans, the inability to regenerate limbs became firmly fixed at the genomic level. The work was supported by the Russian Science Foundation grant 23-74-30005 and published in the journal Biological Reviews. Learn more
Innovative Contact Lenses with Metal-Organic Frameworks for Glaucoma Treatment
Researchers from the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Harvard University, Sechenov University, the Pasteur Institute, and other scientific institutions in Russia and abroad have proposed a new method for controlling elevated intraocular pressure, which is a major damaging factor in glaucoma. They have developed a new type of contact lenses that incorporate metal-organic frameworks (MOFs) for the controlled and prolonged release of brimonidine, a medication used to reduce intraocular pressure. This innovation was presented in the high-ranking scientific journal Aggregate, highlighting its innovative nature and potential impact on ophthalmological practice. Learn more