The arsenolysis reaction in the biotechnological synthesis of ribavirin. The in vitro and in vivo inhibition of influenza A virus replication with a combination of ribavirin and ozeltamivir

The biotechnological method of synthesis of the antiviral drug ribavirin based on the transglycosylation reaction was improved due to the addition of catalytic amounts of sodium arsenate. This approach allows us to hydrolyze the excess natural nucleoside guanosine, a ribose donor, and, hence, made the composition of the reaction mixture less complicated, thus facilitating the process of ribavirin isolation. It was shown that in cell cultures the combination of ribavirin and oseltamivir carboxylate inhibited the replication of the influenza A virus more effectively than each of them alone. Similar results were obtained in experiments on laboratory animals (mouse Balb/c) infected with the influenza A virus H3N2/Aichi/68 strain.