ABSTRACT
With the widespread vaccinations against coronavirus disease 2019 (COVID-19), we are witnessing gradually waning neutralizing antibodies and increasing cases of breakthrough infections, necessitating the development of drugs aside from vaccines, particularly ones that can be administered outside of hospitals. Here, we present two cross-reactive nanobodies (R14 and S43) and their multivalent derivatives, including decameric ones (fused to the immunoglobulin M [IgM] Fc) that maintain potent neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after aerosolization and display not only pan-SARS-CoV-2 but also varied pan-sarbecovirus activities. Through respiratory administration to mice, monovalent and decameric R14 significantly reduce the lung viral RNAs at low dose and display potent pre- and post-exposure protection. Furthermore, structural studies reveal the neutralizing mechanisms of R14 and S43 and the multiple inhibition effects that the multivalent derivatives exert. Our work demonstrates promising convenient drug candidates via respiratory administration against SARS-CoV-2 infection, which can contribute to containing the COVID-19 pandemic.
Subject(s)
COVID-19 , Single-Domain Antibodies , Animals , Mice , Humans , SARS-CoV-2 , Pandemics , Antibodies, Neutralizing , Immunoglobulin Fc FragmentsABSTRACT
The COVID-19 pandemic has endangered human health and production since 2019. As an emerging disease caused by SARS-CoV-2, its potential transmissibility via aerosols has caused heated debate. This work summarizes the current research findings on virus aerosol generation, aerodynamic properties, and environmental influencing factors on their survivability in order to elucidate coronavirus transmission via aerosols. The occurrence and distinction of SARS-CoV-2, SARS-CoV-1, and MERS-CoV in real atmospheric environments are summarized. The deficiencies of existing research and directions for necessary future research on confirming the airborne transmission mechanism of coronavirus as well as the need for multidisciplinary research are discussed.