Anti-SARS-CoV-1 and -2 nanobody engineering towards avidity-inspired therapeutics

In the past two decades, the emergence of coronavirus diseases has been dire distress on both continental and global fronts and has resulted in the search for potent treatment strategies. One crucial challenge in this search is the recurrent mutations in the causative virus spike protein, which lead to viral escape issues. Among the current promising therapeutic discoveries is the use of nanobodies and nanobody-like molecules. While these nanobodies have demonstrated high-affinity interaction with the virus, the unpredictable spike mutations have warranted the need for avidity-inspired therapeutics of potent inhibitors such as nanobodies. This article discusses novel approaches for the design of anti-SARS-CoV-1 and -2 nanobodies to facilitate advanced innovations in treatment technologies. It further discusses molecular interactions and suggests multivalent protein nanotechnology and chemistry approaches to translate mere molecular affinity into avidity.