Targeting the novel coronavirus SARS-CoV-2 using an ancient antibody system

Antibodies are key molecules generated by cells of the immune system involved in the defense against invading pathogens. They are able to bind their targets with a very high degree of specificity. This specific target recognition makes antibodies also valuable reagents in biomedical research as well as in clinical diagnostic and therapeutic applications. While the immune system is capable of generating a vast variety of antibodies, certain targets are difficult to engage either because the protein architecture prevents binding to the target or because the immune system fails to respond to the target. To address this challenge, we propose to harness the variable lymphocyte receptor (VLR) antibody system of the evolutionarily distant jawless sea lamprey. Similar to conventional antibodies, VLR antibodies recognize targets with a high degree of specificity. However, their protein architecture is radically distinct, suggesting that they may detect targets that cannot be recognized by conventional antibodies, a hypothesis supported by studies in our laboratory. We developed an approach to generate specific VLR antibodies. Here we propose to use VLR antibodies to specifically target SARS-CoV-2, the viral pathogen causing Covid-19. Our research will provide a new approach to target the virus, to devise a new class of diagnostic reagent an to explore new vulnerabilities of the viral pathogen.