Antiviral function of pyrrolidine dithiocarbamate against influenza virus: The inhibition of viral gene replication and transcription

Abstract

In summary, the present findings yield the following conclusions: (i) influenza virus-induced moderate ROS overproduction results from apoptosis and it is not responsible for the induction of apoptosis; (ii) PDTC blocks influenza virus-induced apoptosis via the inhibition of viral gene replication and transcription at an early stage of infection rather than through its antioxidant property; (iii) synthesis of specific viral macromolecules at an early stage of infection may play a critical role in the mechanism of apoptosis induction. Finally, virus-induced apoptosis can play a beneficial role in cooperation with the host immune system in the host defence mechanism; in contrast, this process can function in a derogatory capacity, depending on the situation. If virus infection induces massive apoptosis in a broad area of tissue or in essential organs, induction of apoptosis would lead to serious consequences in the infected host. Thus, apoptosis can play a primary role in the pathogenesis of virus. Peptide inhibitors of caspases block the execution of influenza virus-induced apoptosis in vitro but not virus replication.2 Therefore, caspase activation may be involved in the execution of apoptosis by influenza virus infection; however, virus replication may not be directly involved in the process, although it is essential to the induction of apoptosis. It may be said that virus replication is the most important aspect of influenza virus pathogenicity; therefore, genuine anti-apoptosis agents, i.e. caspase inhibitors, may not be suitable for influenza chemotherapy, although these species can block cellular degeneration. Our findings suggest that blockade of influenza virus-induced apoptosis will be achieved via inhibition of viral gene replication and transcription at an early stage of infection as well as via inhibition of virus replication. It is tempting to hypothesize that antiviral drugs such as PDTC may function as future potential anti-influenza drugs.