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1.
Commun Biol ; 5(1): 933, 2022 09 09.
Article in English | MEDLINE | ID: covidwho-2016854

ABSTRACT

Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The nanobodies were collectively shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across existing VoCs; wide-ranging epitopic and mechanistic diversity and high and broad in vitro neutralization potencies. A select set of Fc-fused nanobodies showed high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. In vivo protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a potential therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to combat multiple SARS-CoV-2 variants.


Subject(s)
COVID-19 , Single-Domain Antibodies , Animals , Antibodies, Monoclonal , Cricetinae , Humans , SARS-CoV-2/genetics , Single-Domain Antibodies/genetics
2.
Can Urol Assoc J ; 15(6 Suppl 1): S16-S19, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1278661

ABSTRACT

The arrival of COVID-19 modified the way we live, care, teach, and self-care tremendously. Indeed, our personal and professional lives were much affected, and despite the fact that Canadian healthcare workers (HCW) and systems had some time to prepare in comparison to other countries, we faced a scenario that resembled no other. Adding the negative effects of a never-before-seen pandemic to the already well-known risk of burnout among HCW could surely increase the likelihood of colleagues, as well as ourselves, being affected. We hereby reviewed the numerous factors that could increase the risk of burnout amid this ongoing pandemic.

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