[A050] Proteolysis Inhibitor E-Aminocaproic Acid as Effective Drug for Prevention and Treatment of Influenza, Other Acute Respiratory Viral Infections and their Bacterial Complications
2 I.I. Mechnikov Ukrainian Anti-Plague Research Institute, Ministry of Health, Odessa, Ukraine
3 Odessa National Medical University, Odessa, Ukraine
4 State Enterprise “Research Enterprise Institute of Chemical Technology “Chemtechnology”, Sevtodonetsk, Ukraine
5 Ukrainian Military Medical Academy, Kyiv, Ukraine
6 L.V.Gromashevsky Institute of E pidemiology and Infectious Diseases of NAMS of Ukraine, Kyiv, Ukraine
7 Military Medical Clinical Center of the Western Region, Lviv, Ukraine
* Author to whom correspondence should be addressed.
The proteolytic cleavage is the universal mechanism of specific proteins activation. The activation of proteolysis plays an important role in the pathogenesis of many diseases including viral infections. The results of our research and the scientific data have made it possible to formulate the concept of formation of a “vicious circle”: virus activates the proteolytic systems, which in turn assists the development, generalization, and aggravation of the infectious process at the expense of influence on the etiological and pathogenetical factors. Inhibitors of proteolysis (IP) may prevent the formation or destroy this “vicious circle”. Usually IP E-aminocaproic acid (name of medicine “Aminocaproic acid” - ACA) is used for hemostasis when fibrinolysis contributes to bleeding. ACA is a low toxic drug. The intravenous and oral LD50 of ACA are 3.0 and 12.0 g/kg respectively in mice. ACA prevents the enhancement of proteolysis during the interaction of virions with cell membranes and decreases penetration of virions into sensitive cells. It brings down proteolytic cleavage of HA precursor to HA-1 and HA-2 and reduces the infectious virus harvest. It has been shown that, in vitro, ACA exhibits high levels of anti-influenza efficacy on subtypes H1N1; H2N2; H3N2 of human, H5N3 and H7N3 avian influenza A viruses and on influenza B viruses. ACA promotes the intensification of specific antibodies production and cell immunity, prevents vessels permeability and hemorrhagic phenomena and decreases the destruction of bronchi epithelium. Mice treated by ACA after primary infection were more protected to re-infection. ACA decreased the virus reproduction in lungs and also enhanced the humoral immune response when used in the prevention and treatment of influenza. Farmaceutic Center and Ukrainian Ministry of Public Health, on the basis of our experimental research and clinical trials, have allowed using ACA as antiviral for prevention and treatment of influenza and other acute respiratory viral infections (ARVIs) in children and adults. The results of including ACA in the therapeutic complex for treatment of influenza and other ARVIs in children were: decrease of duration of intoxication symptoms on 2-3 days, of fever on 1.5-3 days, of catarrhal symptoms on 1.5-2 days. Number of complications was reduced to 17%. Prophylactic efficacy of ACA was also established. With the scope to study the ACA prophylactic activity in organized collectives, we have prescribed it per-orally in 2.0 g dose four times a day during a week. The monitoring was performed in two independent collectives (923 young adults males aged 18-19 years old) during acute respiratory diseases appraisal. As the reference, 4 groups were taken (2 from each collective) but without ACA application. The obtained results show: compare to the high morbidity rates in the reference group of the first tested collective in the basic group preventively treated with ACA, number of ARVIs has decreased in two-fold. At the same time, compare to the morbidity rate growth of ARVIs (by 15-27%), quinsy (by 14-21%) and pneumonia (by 6-7%) in the reference groups of the second tested collective, of the main examined group treated with ACA, pneumonia morbidity rate has decreased up to five-fold, while the ARVIs and quinsy levels were stabilized. The smallest number of cases of these infections in both teams surveyed was recorded in the period of ACA application. The obtained results allow to recommend the use of ACA for the efficient prophylaxis of ARVIs, quinsy and pneumonia in the organized collectives in the period of increased incidences of these infections. It is known that use of agents with different mechanisms of antiviral actions may have as result synergistic effects. Our studies of anti-influenza activity in vitro and in vivo show that the results of combined action of ACA with Tamiflu are synergistic antiviral effects. We have studied the influence of ACA on the growth of S.aureus. Strains АТСС 25923, 2781 and Kunda of Staphylococcus aureus were used. It was stated that ACA taken in final concentration of 15, 10 and 7.5%, has hindered the growth of S.aureusАТСС 25923 totally. It is known that the IP increases the sensitivity of some microorganisms to antibiotics. We have shown that ACA inhibits the reproduction of various strains of S.aureus that have different sensitivity to antibiotics. ACA can strengthen the antimicrobial action of antibiotics against the studied strains of Staphylococcus aureus. So use of ACA for treatment of influenza and other ARVIs simultaneously prevents bacterial complications.
Conclusion E-aminocaproic acid is an effective remedy for prevention and treatment of influenza and acute respiratory viral infections in children and adults and simultaneously for prevention of bacterial complications. The combination of proteolytic inhibitor E-Aminocaproic acid with neuraminidase inhibitor Tamiflu constitutes a promising perspective in anti-influenza protection and therapy.