In this study, we demonstrate the concept of "topology-matching design" for virus inhibitors. With the current knowledge of influenza A virus (IAV), we designed a nanoparticle-based inhibitor (nano-inhibitor) that has a matched nanotopology to IAV virions and shows 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 when used 24 hours after the infection, more than 99.999 % inhibition is still achieved, which indicates such a nano-inhibitor might be a potent antiviral for the treatment of influenza infection.
Influenza meets its match: Based on the principle of topology matching, a potent nanoparticle‐based inhibitor for influenza A was designed that shows heteromultivalent inhibition of the receptor‐binding viral proteins. This inhibitor is capable of neutralizing influenza A virus extracellularly and blocking its interaction with the host cell receptors. This principle could potentially also be applied to the inhibition of other viruses with spiky surfaces.
Keywords: antiviral agents; influenza; inhibitors; nanoparticles; topology matching.
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.