Attempts to develop highly efficient and cost-effective drugs for COVID-19 have met many challenges. Nanobodies are single-domain antibody fragments, that bind selectively to a specific antigen. For anti-SARS-CoV-2, these nanobodies are generated such that they primarily target the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein for virus neutralization. Nanobodies are found to have high neutralization potency and are cheaper to produce. A paper published on the preprint server has presented results of a stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21) against SARS-CoV-2 infection in Syrian hamsters.
They demonstrated the high therapeutic efficacy of this homotrimeric Nb, leveraging both intranasal and aerosol delivery. The researchers used Syrian hamsters for the in vivo studies. The Syrian hamsters model moderate to severe COVID-19 disease. The PiN-21 was delivered intranasally and via inhalation. Consistent protection and a reduction of the viral genomic RNA (gRNA) by reverse transcriptase (RT)-qPCR was observed in these animals. On day two post-injection, the virus was undetectable in the upper respiratory tract (URT), including both nasal washes and throat swabs of all the PiN-21-treated animals. In contrast, the control group presented varying levels of infectious virus.
The researchers reconstructed the PiN-21 for aerosolization and found that it retained high neutralization potency. Critically, the researchers observed that the aerosolization treatment diminished the infectious viruses in the lung, indicating that the Nb administration by aerosolization may limit human-to-human transmission of SARS-CoV-2.
The researchers have found that the PiN-21 can efficiently protect SARS-CoV-2 infection in hamsters by rapidly and drastically suppressing viral replication in both the URT and lower respiratory tract (LRT). Importantly, the researchers underscored the requirement of an ultra-low dose of the PiN-21 construct to neutralize SARS-CoV-2 infectivity in vivo efficiently.