Ingavirin

Repurposing therapeutic agents with existing clinical data is a common strategy for developing radiation countermeasures. IEPA (imidazolyl ethanamide pentandioic acid) is an orally bioavailable small molecule pseudopeptide with myeloprotective properties, a good clinical safety profile, and stable chemical characteristics facilitating stockpiling. Here, we evaluated IEPA's radiomitigative efficacy in the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) using total-body irradiation (TBI) models in C57BL/6J mice and WAG/RijCmcr rats, applying various posology schemes and introducing syringe feeding of the IEPA formulation in the pudding. Additionally, we assessed IEPA in the delayed effects of acute radiation exposure (DEARE) model after partial-body irradiation (PBI) in WAG/RijCmcr rats. Endpoints included survival, body weight, hematology, and pulmonary parameters, depending on the model. Results from mouse and rat TBI models demonstrated survival improvements with repeated IEPA dosing at 10 mg/kg, with the largest benefits observed in the bi-daily (BID) treatment over the 30-day ARS phase in female rats. Survival across PBI-DEARE subsyndromes was comparable between IEPA and vehicle groups, though IEPA improved pulmonary parameters in female rats during the lung-DEARE phase. Sex-related differences in response to irradiation and IEPA were noted, with females showing a survival advantage. IEPA treatment is compatible with Neulasta® (Pegfilgrastim; PEG-G-CSF); adequately powered studies are needed to confirm the trend toward improved survival over standard care alone. IEPA is a promising development candidate as a medical countermeasure against the effects of acute radiation syndrome. Further confirmatory studies in small and large animal models should validate the robustness and translatability of preliminary rodent data on IEPA's radiomitigative efficacy.

The Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease-19 (COVID-19) pandemic, caused by the virus, have changed the world in just half a year.Lack of effective treatment, coupled with etiol. of COVID-19, has resulted in more than 500,000 confirmed deaths at the time of writing, and the global economy is at an unseen unprecedented low level with unknown near- and long-term consequences.Ingavirin has been considered a non-toxic broad-spectrum antiviral with a complex mechanism of action.The mol. was originally designed for the prophylaxis and treatment of flu caused by both Influenza A and B viruses and for the treatment of viral causes of acute respiratory illness.The article hypothesized that the efficiency of given 1H-imidazol-4-yl heterocyclic scaffold-containing compound against SARS-CoV-2 might be connected with its ability to interfere with specific heterogeneous nuclear ribonucleoproteins (A1, for example).These specific cellular RNA-binding proteins showed affinity to Severe Acute Respiratory Coronavirus (SARS-CoV) nucleocapsid (N) protein, which shared high homol. with the N protein of SARS-CoV-2 and the fact was expressed by a sequence identity of 90.52%.Impairing of the interactions between nuclear ribonucleoproteins and nucleocapsid (N) protein of SARS-CoV-2 might result in the inhibition of a viral replication cycle.Addnl. immunomodulating properties of ingavirin could be favorable for induction of adaptive immunity of host cells.