Activity of Ingavirin (6-[2-(1H-Imidazol-4-yl)ethylamino]-5-oxo-hexanoic Acid) Against Human Respiratory Viruses in in Vivo Experiments

Abstract

Respiratory viral infections constitute the most frequent reason for medical consultations in the World. They can be associated with a wide range of clinical manifestations ranging from self-limited upper respiratory tract infections to more devastating conditions such as pneumonia. In particular, in serious cases influenza A leads to pneumonia, which is particularly fatal in patients with cardiopulmonary diseases, obesity, young children and the elderly. In the present study, we show a protective effect of the low-molecular weight compound Ingavirin (6-[2-(1H-imidazol-4-yl)ethylamino]-5-oxohexanoic acid) against influenza A (H1N1) virus, human parainfluenza virus and human adenovirus infections in animals. Mortality, weight loss, infectious titer of the virus in tissues and tissue morphology were monitored in the experimental groups of animals. The protective action of Ingavirin was observed as a reduction of infectious titer of the virus in the lung tissue, prolongation of the life of the infected animals, normalization of weight dynamics throughout the course of the disease, lowering of mortality of treated animals compared to a placebo control and normalization of tissue structure. In case of influenza virus infection, the protective activity of Ingavirin was similar to that of the reference compound Tamiflu. Based on the results obtained, Ingavirin should be considered as an important part of anti-viral prophylaxis and therapy.

The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design

“…F), a controversial influenza inhibitor that is commercially available in Russia. This agent was reported to impair biogenesis and oligomerization of NP in vitro and suppress influenza A and B infections in animal models . However, since its broad antiviral activity encompasses unrelated respiratory viruses, Ingavirin® most likely targets a cellular rather than a virus‐specific component.…”

Strategies for the Development of Influenza Drugs: Basis for New Efficient Combination Therapies

“…Meanwhile, the imidazole derivative ingavirin (51) is an approved anti-influenza drug in Russia [89]. Although its mechanism of action is not absolutely clear, it was suggested that ingavirin also interacts with the influenza virus NP, thus preventing the NP oligomerization necessary for viral replication [90].…”

Synthesis and Comparative Study of Anti-Adenoviral Activity of 6-Azacytidine and Its Analogues

“…[6,7] More recent research on antiviral properties of 6-azaСyd has demonstrated its high activity relative to human AdV in vitro and in vivo systems. [8][9][10][11][12][13] In cell cultures, the anti-adenoviral effect of 6-azaСyd was expressed by inhibiting the formation of virus-specific intranuclear DNA-containing inclusion bodies, the synthesis of viral proteins and infectious virus. [12,14] The application of 6-azaСyd on a model of disseminated AdV infection in newborn Syrian hamsters led to significant decrease of virus titer and shortening of the time of virus clearance in organs.…”