Aptamers to Hemagglutinin: A Novel Tool for Influenza Virus Recognition and Neutralization

Influenza virus can cause epidemics and pandemics of flu. A highly variable virus genome is responsible for the existence of different viral strains and acquired resistance to antiviral drugs. Today, only one class of therapeutics, neuraminidase inhibitors, is efficient and proved for influenza prophylaxis and treatment; whereas M2 protein inhibitors became inefficient due to evolving drug resistance. Therefore, there is an urgent need for the development of novel therapeutics. Aptamers are promising molecular recognition elements of high specificity and low toxicity, but only a few of them are under development as therapeutics. After selection of primary aptamers, there are sophisticated steps of further adjustments to the target and meeting requirements for therapeutics. In the last decade, dozens of DNA and RNA aptamers to various influenza types have been selected, but no comparative analyses have been performed yet. Most of aptamers were selected to hemagglutinin, a viral surface protein, which supports the first stages of virus invasion into the host cell. In the review, all available data on aptamers to hemagglutinin are analyzed. Aptamer specificity and affinity are discussed, as well as examples of aptamer applications for virus detection and virus infection inhibition. In summary, aptamers can be selected for hemagglutinin recognition, aptamers to hemagglutinin can recognize viruses with different specificity, and some aptamers can neutralize virus in vitro, ex vivo and in vivo. Special sections of the review are dedicated to the original structural analyses. Some structural similarities among different aptamers have been revealed suggesting involvement into the target recognition.