Small synthetic molecules provide valuable tools to agricultural biotechnology to circumvent the need for genetic engineering and provide unique benefits to modulate plant growth and development. We developed a method to explore molecular mechanisms of plant growth by high-throughput phenotypic screening of haploid populations of pollen cells. These cells rapidly germinate to develop pollen tubes. Compounds acting as growth inhibitors or stimulators of pollen tube growth are identified in a screen lasting not longer than 8 h high-lighting the potential broad applicability of this assay to prioritize chemicals for future mechanism focused investigations in plants. We identified 65 chemical compounds that influenced pollen development. We demonstrated the usefulness of the identified compounds as promotors or inhibitors of tobacco and Arabidopsis thaliana seed growth. When 7 days old seedlings were grown in the presence of these chemicals twenty two of these compounds caused a reduction in Arabidopsis root length in the range from 4.76 to 49.20 % when compared to controls grown in the absence of the chemicals. Two of the chemicals sharing structural homology with thiazolidines stimulated root growth and increased root length by 129.23 and 119.09 %, respectively. The pollen tube growth stimulating compound (S-02) belongs to benzazepin-type chemicals and increased Arabidopsis root length by 126.24 %. In this study we demonstrate the usefulness of plant pollen tube based assay for screening small chemical compound libraries for new biologically active compounds. The pollen tubes represent an ultra-rapid screening tool with which even large compound libraries can be analyzed in very short time intervals. The broadly applicable high-throughput protocol is suitable for automated phenotypic screening of germinating pollen resulting in combination with seed germination assays in identification of plant growth inhibitors and stimulators.

COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir^® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry of Health for the treatment therapy of moderate COVID-19 patients. This prospective single-center study included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU four times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). In cohorts 1–3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of the combination therapy in cohort 3 was the most prominent, and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0–4.0), normalization of the CRP concentration was 3.5 days (IQR 3–5), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1–3), improvement in clinical status or discharge from the hospital was 5 days (IQR 5–5), and improvement in lung lesions of patients on 14 day was 100%.

In May 2020 the Russian Ministry of Health granted fast-track marketing authorization to RNA polymerase inhibitor AVIFAVIR (favipiravir) for the treatment of COVID-19 patients. In the pilot stage of Phase II/III clinical trial, AVIFAVIR enabled SARS-CoV-2 viral clearance in 62.5% of patients within 4 days, and was safe and well-tolerated.

Selective inhibition of poly(ADP-ribose) polymerase 1 (PARP1) may reduce the hematologic toxicity associated with dual PARP1/PARP2 inhibition. We performed molecular dynamics simulations for five selective inhibitors in complexes with PARP1 and PARP2, using three independent 50 ns runs per complex after docking and equilibration, followed by protein–ligand interaction fingerprint and statistical analyses. All complexes remained dynamically stable, with ligand root-mean-square deviation values generally within 0.3 nm. Comparative analysis identified three αF-helix residue pairs with nominally reduced interaction frequencies in PARP2: Asn767/Ala336, Leu769/Gly338, and Asp770/Asp339 (p < 0.05). After Benjamini–Hochberg correction for multiple comparisons, Leu769/Gly338 remained significant (q < 0.05), indicating that this pair represents the most statistically robust interaction difference within this region. Using palacaparib as the most selective inhibitor, these differences were associated with weakened or lost hydrophobic, van der Waals, and cation–π interactions in PARP2. Selective binding of modern PARP1 inhibitors appears to be associated with αF-helix-dependent interaction patterns, providing a mechanistic basis for the rational design of next-generation selective inhibitors with improved selectivity and potentially reduced toxicity.

Trends Psychiatry Psychother, vol.0, nAheadOfPrint, p.0-0, 2025