Nanobodies, the antibody fragments that share an ability to bind with antigens that trigger immune responses, have the potential to combat replication of the COVID-19 (SARS-CoV-2) virus, according to newly-published research by an international team of researchers led by NYUAD’s Associate Dean for Research and Graduate Programs, Science Division; Program Head, Biology and Associate Professor of Biology Piergiorgio Percipalle and Visiting Professor of Chemistry Gennaro Esposito.
While other research has explored how nanobodies might be generated against the surface-exposed portion of the spike protein with the aim of blocking viral entry in the host cells, Esposito, Percipalle, and their colleagues sought to identify other potential targets for the development of nanobodies that could have potential use in diagnostics, and possibly, treatment.
In the study, NMR-based analysis of nanobodies to SARS-CoV-2 Nsp9 reveals a possible antiviral strategy against COVID-19, which appears in the journal Advanced Biology, the researchers report that they generated nanobodies against the SARS-CoV-2 non-structural protein Nsp9, a key component of the Replication Transcription Complex (RTC) required for SARS-CoV-2 replication. In immunoassays, they demonstrated that two of these nanobodies, 2NSP23 and 2NSP90, specifically reacted with purified recombinantly-expressed Nsp9 and with endogenous Nsp9 in the saliva of COVID-19 patients. Nuclear Magnetic Resonance (NMR) analysis supported by molecular dynamics showed that Nsp9 has a composite oligomerization pattern, and demonstrated that both nanobodies stabilize the tetrameric form of Nsp9, identifying also the epitopes on the tetrameric assembly.
“We believe our study identifies Nsp9 as a novel druggable target that, in the long term, may be a valid alternative to design new antiviral strategies, for both diagnosis and treatment,” said Esposito.