Nasal Delivery of Encapsulated Recombinant ACE2 as a Prophylactic Drug for SARS-CoV-2

ALBERTO BALDELLI, Hale Oguzlu, Yigong Guo, Hui Xin Ong, Daniela Traini, Anubhav Pratap-Singh, The University of British Columbia

     Abstract Number: 9
     Working Group: Aerosol Science of Infectious Diseases: What We Have Learned and Still Need to Know about Transmission, Prevention, and the One Health Concept

Abstract
Covid-19 has caused a global pandemic, and worldwide, the number of deaths exceeded five million. Even though medical research efforts have developed vaccines, vaccination worldwide faces several challenges. As well, several mutations can jeopardize the efficacy of these vaccines. Most research studies the production of a vaccine that uses intravenous (IV) or intramuscular delivery to boost. For such a purpose, one might think that the most logical approach would be to decrease or repress the number of cell receptor ACE2. While as humans, our heart and lung produce soluble ACE2, a recombinant form of the cell receptor Angiotensin-Converting Enzyme2 (rhACE2) version is accessible on the market. rhACE2 can serve as an interceptor of SARS-CoV and other selected coronaviruses by binding to the surface of the viral particle. We aim to develop a non-invasive drug involving the advantages of rhACE2 against SARC-CoV-2. Spray freeze drying (SFD) is the only spraying technique that allows the control over the properties of sprayed powders and the use of low temperatures. The affinity of rhACE2 and the spikes protein of SARS-CoV-2 has already been explored, and the idea of using rhACE2 as a possible treatment of Covid19 has been published in a few research studies. However, the concept of generating an inhalable form of rhACE2 to be delivered to the nasal cavity as prophylactic is new. We encapsulated rhACE2 maintaining its stability and affinity with spike proteins of SARS-CoV-2 at 97 and 82 %, respectively. Using the MTS assay, we demonstrated that rhACE2 protein does not negatively affect Calu-3 and RPMI-2650 cell viability. We ultimately show that the encapsulation procedure enhances the cellular uptake by 93 %.