The resilience of Ukrainian scientists.

We have asked Ukrainian scientists how they have been able to persist in pursuing their research since the beginning of the full-scale invasion of Ukraine by the Russian Federation in February of 2022. We thank the scientists who were willing to share their thoughts and experiences; the views expressed are those of the contributors alone.

In vitro and in silico studies of the antiviral activity of polyhydrated fullerenes against influenza A (H1N1) virus.

As of today, influenza viruses remain a relevant target for the development of antiviral compounds due to their rapid evolution and acquisition of the resistance to existing drugs. Fullerene derivatives have already shown the ability to successfully interact with viruses, and polyhydrated fullerenes (or fullerenols) are particularly attractive due to their compatibility with biological fluids and low toxicity. Therefore, the goal of this work was to study the effect of two batches of a mixture of polyhydrated fullerenes with a mass ratio of 78.1% C60/C70 and 21.9% C76/C78/C84 on the influenza A (H1N1) virus. It was determined that the mixture of fullerenols, along with the low toxicity, showed high antiviral activity with a decrease in the viral infectious titer up to 4 orders of magnitude. In addition, studied fullerenols did not affect the hemagglutination process and did not show any significant prophylactic activity. With the help of molecular docking and molecular dynamics simulation, the likely target of fullerenols' action was determined-the binding site of the RNA primer of the viral RNA-dependent RNA polymerase. Therefore, we assume that the high antiviral effect of polyhydrated fullerenes on influenza A virus is related to their interaction with the viral RNA polymerase.

In silico study of HASDI (high-affinity selective DNA intercalator) as a new agent capable of highly selective recognition of the DNA sequence.

Cancer as an acquired genetic disease is based on changes both in the genome itself and in transcription processes. Accordingly, it is at the DNA level that it makes sense to search for and design agents capable of effective and selective anticancer action. In this study, we used an iterative approach based on a molecular dynamics simulation to design a highly selective DNA-intercalating agent called HASDI. To confirm its selective affinity to DNA, we conducted two simulation experiments: HASDI in a complex with a DNA fragment of the EBNA1 gene (it targets 16 nucleotide pairs of this gene) and HASDI in a complex with a random DNA fragment of the KCNH2 gene. The molecular dynamics simulation was carried out in the GROMACS 2019 package. The binding energy was calculated by gmx_MMPBSA 1.5.2. The further analysis was performed using the built-in utilities of GROMACS, gmx_MMPBSA and also XMGRACE and Pymol 1.8. As a result, we determined that the EBNA1-50nt/HASDI complex was stable throughout the whole simulation trajectory. HASDI, due to the presence of a linker modified depending on a specific pair of nitrogenous bases, formed an average of 32 hydrogen bonds with a sequence of 16 nucleotide pairs. Phenazine rings were stably intercalated every 2 base pairs. The root-mean-square deviation of HASDI in such a complex fluctuated around the value of 6.5 Å and had no tendency to increase. The calculated value of the binding free energy was - 235.3 ± 7.77 kcal/mol. The KCNH2-50nt/HASDI complex, as an example of the intercalation of the designed structure into a random part of the human genome, maintained the stability of its position at a level comparable to the EBNA1-50nt/HASDI complex. The phenazine rings were constantly intercalated in their original positions, and the root-mean-square deviation fluctuated around one value, although it had a tendency to chaotic changes. At the same time, this complex was characterized by 17-19 hydrogen bonds, on average, and the binding free energy was - 193.47 ± 14.09 kcal/mol. Moreover, the DNA duplex had local single-nucleotide melting in the region of the 4th linker. According to a significant decrease in the number of hydrogen bonds, a decrease in energy gain, as well as a decrease in the stability of the DNA duplex characteristic of the KCNH2-50nt/HASDI complex compared to the target EBNA1-50nt/HASDI complex, the molecule we designed can be considered a potentially selective DNA polyintercalating agent capable of relatively accurate recognition of 16 base pairs.

Continuity of operations over repeated crises. Case study of the biggest Ukrainian CRO.

Pharmaxi (hereinafter CRO) is a Ukrainian group of companies providing full service in clinical trials. At the beginning of the massive military Russian invasion of Ukraine on the 24th of February 2022, it was the biggest CRO in Ukraine with 17 full-time employees and 8 contractors. Founded in 2013, it has grown up increasingly while building resilience to repeated crises in Ukraine, sustaining continuity of operations. The company evolved through political instability during the Revolution of Dignity, the subsequent beginning of the Russian occupation of Crimea, the beginning of hybrid armed conflict in the Eastern part of Ukraine in 2014, and the COVID-2019 crisis. In the sixth month of the active Russian-Ukrainian war, the company continues business operations and is ready for further development. This case study investigates the strategy and best practices for ensuring business stability through contingency, resilience, and recovery actions analysis, expert interviews with management, and the SWOT analysis of the study findings. In particular, the organisational continuity framework features financial policy, human resources management, organisational behaviour practices, internal communication, and diversification. While investigating the case of company's continuity of operations, it appeared that the company had a crosscutting orientation on stability. The core domains ensuring resilient company's activity over repeated crises were the diversification, utilization tools for financial stability, distinct human capital management and design of operations. Study's results might be relevant to small and middle-sized service companies.

De novo designed EBAI as a potential inhibitor of the viral protein BHRF1. Research in silico.

Epstein-Barr virus is a DNA-containing virus that, according to current data, is associated with approximately 1% of all cancers in the world. This viral effect on the human body is associated with its pronounced antiapoptotic activity. An important role in this process is played by the protein BHRF1, which is a structural and functional homologue of antiapoptotic proteins of the BCL-2 family. In this study, we investigate the selective low molecular weight inhibitor of the above viral protein - EBAI (Epstein-Barr virus Antiapoptotic Inhibitor), which we designed using in silico methods. We conducted two parallel simulation experiments where EBAI was intentionally destabilized to demonstrate its high-affinity recognition potential of the BHRF1 pocket, which binds BH3.Thus, although the potential inhibitor was in close proximity to the site of interaction, it contacted it only through orientation interactions (hydrogen and Coulomb interactions). Despite this complication of the standard ligand-receptor complex simulation procedure, we demonstrated in two parallel computational experiments the high affinity of EBAI for the BH3-binding pocket of BHRF1. In both cases, in the first nanoseconds of modeling, our inhibitor underwent the necessary conformational rearrangements and formed all the required interactions for effective complexation. Thus, further in vitro studies are logical and necessary step to fully evaluate the potential of EBAI as an inhibitor of the antiapoptotic protein BHRF1 of Epstein-Barr virus.Communicated by Ramaswamy H. Sarma.

De novo designed inhibitor has high affinity to four variants of the RBD of S-glycoprotein of SARS-CoV-2 - an in silico study.

In the years since the rapid invasion of SARS-CoV-2, the world community has fully understood the extent of the danger of this new pathogen. And also the speed with which he is able to adapt both to humans as a species and to the means of combat that are introduced. However, this has already resulted in millions of lost lives and this situation may worsen in the future, due to the further inevitable evolution of the virus. Accordingly, the need for effective drugs is urgent. In this work, using an iterative approach, we de novo designed a molecule that revealed significant affinity to four variants of SARS-CoV-2 - Wuhan, Omicron, Delta and Cluster 5. More precisely, to their receptor-binding domain of S-glycoprotein, in particular, to the site that is directly involved in the recognition of human ACE2.What is confirmed in particular by the ΔGbind of the complexes of RBD of all four SARS-CoV-2 variants with a potential inhibitor: it is in significantly negative values. Along with this, the calculated ADMET parameters can generally be considered acceptable. Accordingly, we believe that the molecule we have designed has a high potential for further development as an effective drug against SARS-CoV-2. However, it currently requires further in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.