Project 2: Nanobodies as Novel Entry Inhibitors of Pandemic Viruses Abstract

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Construction of a camelid nanobody phage display library and use of this library for screening of anti-SARS-CoV-2 nanobodies.

Project 2: Nanobodies as Novel Entry Inhibitors of Pandemic Viruses Abstract

Nanobodies are single-domain antibodies derived from camelid antibodies. Due to their small size, nanobodies have many advantages over conventional human antibody therapeutics. Such benefits include their ability to bind onto targets, ease of production, superior ability to move through the body, and strong physical and chemical stability. They also have high on-target specificity and low side effects.

The fast emergence of SARS-CoV-2 variants calls for the urgent need for potent and broad-spectrum anti-COVID-19 therapeutics. Compared to small-molecule antiviral drugs, nanobodies can be adapted quickly to new viral variants.

In our prior studies, we have developed several potent anti-Covid-19 nanobodies, including a series of drug candidates named Nanosota-1.

Our project has three specific aims. Our first aim is to screen antiviral nanobodies for protein interactions. We will also use in vitro techniques to optimize the strength of those interactions.

Our second aim is that we will engineer nanobodies to further improve their antiviral potency. We will also enhance a nanobody’s ability to move through the body and minimize its side effects.

In our third aim, we will test and validate nanobody candidate drugs in animal models against viral infections.

This project is built upon a strong research team with complementary expertise in coronaviruses, filoviruses, arenaviruses, and flaviviruses, solid preliminary data, well-established platforms, and full support from the administration, chemistry, structural biology, and virology cores.