3.2 In vitro inhibitory effects of aprotinin on
infections caused by various influenza A virus subtypes
Previous studies have minimal information on the spectrum of the
anti-influenza viral activity of aprotinin. Therefore, we evaluated the
effects of aprotinin treatment on the production of infectious particles
of various IAV subtypes, including human and avian viruses, through
time-based studies by determining the growth kinetics of the following
viruses in MDCK cells: A/PR/8/34 (H1N1), A/CA/04/09 (H1N1), A/PH/2/82
(H3N2), A/AB/Kor/CN2/09 (H5N2), A/AB/Kor/CN5/09 (H6N5), and
A/Ck/Kor/01310/01 (H9N2) viruses. We simultaneously added each virus and
60 nM aprotinin to the cell cultures and cultured without removing
either virus or aprotinin throughout the incubation period. Culture
supernatants were collected at different time points, and virus titers
were determined by calculating the median TCID50 based
on the hemagglutination assay. As shown in Fig. 3, aprotinin was able to
significantly reduce the production of the tested human IAVs after more
than 16 h post-infection, supporting the results of previous
studies.[17,19] Especially, aprotinin had superior inhibitory
effects on A/CA/04/09 (H1N1) and A/PH/2/82 (H3N2) viruses than
oseltamivir. Aprotinin was also able to significantly reduce the
production of the tested avian IAVs (Fig. 4). Aprotinin displayed weaker
inhibitory effects on avian IAVs than oseltamivir at early time points
post-infection but presented similar effects to oseltamivir at 64 h
post-infection. These results indicate that aprotinin had inhibitory
effects on infections of both human and avian IAVs.