In vitro study of anti-influenza activity of para-aminobenzoic acid and prospects of nasal drug development on its base

Abstract

One of the promising molecules having antiviral activity is a vitamin-like substance, para-aminobenzoic acid (PABA). The aim of this work is to study antiviral activity of para-aminobenzoic acid, ε-aminocaproic acid, and their mixture against influenza virus, to evaluate their cytotoxic effect and to calculate their selectivity index by in vitro methods. Materials and Methods. For evaluation of cytotoxic concentration (CC₅₀) of the substance tested, we used MDCK cell culture. For determination of anti-influenza activity of PABA, ε-АCA, and their mixture under conditions of in vitro experiment, we used 24-hour passaged MDCK culture cells of dog’s kidney, influenza virus strain А/FM/1/47 (H₁N₁), infected titer of which in MDCK culture cells of was between 3.0 and 9.0 lgID₅₀. Results. As a result of our studies, we have determined that PABA in the concentration range studied from 10 to 1,000 ug/ml did not have any cytopahtic effect in MDCK culture cells. We calculated selectivity index (SI) for PABA, that was equal SI=128205, this fact confirm high level of therapeutic safety of this substance. The result of our experiments demonstrate that anti-influenza activity of PABA solution is almost 100 times higher than that of “ACA”, furthermore in our in vitro experiment the mixture of PABA and ε-aminocaproic acid (in ratio 1:100) demonstrates a synergetic effect. In addition, for combination of PABA and εАКК (1:100) we calculated fractional inhibitory coefficient FIC=0.79, that indicates to moderate synergetic effect of these substances. Conclusions. As a result of our in vitro studies, we have determined a high-level antiviral activity of para-aminobenzoic acid against influenza virus, and in combination with ε-aminocaproic acid it demonstrated a synergetic effect. We have determined that PABA does not exhibit any cytotoxic effect on MDCK culture cells in the concentration range studied and demonstrates high level of therapeutic safety.