Reverse design of an influenza neutralizing spiky nano‐inhibitor with a dual mode of action

Nie, Chuanxiong; Parshad, Badri; Bhatia, Sumati; Cheng, Chong; Stadtmüller, Marlena; Oehrl, Alexander; Kerkhoff, Yannic; Wolff, Thorsten; Haag, Rainer

In this study, we demonstrate the concept of ‘reverse design’ for virus inhibitors. With the current knowledge of influenza A virus (IAV), we designed a nano‐inhibitor that has a reverse shape to the viral particle and heteromultivalent inhibitory effects on hemagglutinin and neuraminidase. The synthesized nano‐inhibitor can neutralize the viral particle extracellularly and block its attachment and entry to the host cells. The virus replication was significantly reduced by 6 orders of magnitude in the presence of the reverse designed nano‐inhibitors. Even being used 24 hours after the infection, >99.999% inhibition is also achieved, which indicates such a nano‐inhibitor might be a potent antiviral for the treatment of influenza infection.