Design of targeted antiviral polypeptides specific to SARS-CoV-2. Challenges and prospects

Abstract

The COVID-19 epidemic demanded the rapid development of high-affinity molecules of different types aimed at a single target, the S-protein of SARS-CoV-2. The simultaneous development and testing of such molecules provide a unique opportunity to compare the features of biotechnological platforms for creating therapeutic proteins. This review considers classical antibodies, variable lymphocyte receptors, single-domain antibodies, and artificial scaffolds (DARPins, affibodies, VH), that are compared in terms of affinity, neutralizing activity, size and compatibility with different delivery methods. It can be concluded that all platforms used have produced high-affinity proteins that specifically bind to the coronavirus S-protein. The highest affinity of the targeting molecules with the virus protein was achieved by developing classical antibodies, nanobodies and by combining several binding modules into multivalent constructs with high avidity. Based on the results of <i>in vivo</i> experiments, it can be concluded that a high affinity of the therapeutic protein for the surface antigens of SARS-CoV-2 is a necessary but not sufficient condition for suppression of COVID-19 due to the peculiarities of the biology of this virus. The experience gained in the development of therapeutic agents against coronavirus will be useful for design of effective targeted drugs for the treatment of known and new viral infections.<br>The bibliography includes 126 references.