By Dr. Chinta SidharthanSep 20 2022Reviewed by Danielle Ellis, B.Sc. In a recent study posted to the bioRxiv* preprint server, researchers investigated nanobody engineering to develop antivirals and diagnostic tools against severe acute respiratory syndrome coronavirus 2 .
Current research against the immune evasion exhibited by some of the new SARS-CoV-2 variants is focused on developing new antibody-based technology such as camelid single-domain antibody fragments or nanobodies. While a few SARS-CoV-2-neutralizing nanobodies have been characterized, the use of nanobodies in diagnostic tools remains largely unexplored.
Furthermore, the modular properties of nanobodies were used to develop a diagnostic assay consisting of RBD-binding nanobodies fused with split fragments of the engineered fluorescent luciferase protein NanoLuc, which acts as the signal molecule. The diagnostic assay is based on the principle that when the split fragments of NanoLuc are brought into proximity by the binding of the nanobodies to the SARS-CoV-2 spike trimers, the fusion of the fragments will result in a fluorescent signal.
According to the authors, the E484K mutation present in the Beta and Omicron variants but absent in wild-type SARS-CoV-2 and the other variants is responsible for the reduction in the efficacy of the three nanobody constructs. This mutation results in changes in the amino acids, which disrupt the salt bridges and cause conformational changes in the RBD, thus affecting the nanobody binding interface.
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