A breathable virus decoy

Angiotensin-converting enzyme 2 (ACE2) is proven to be the key in SARS-CoV-2 infection process, due to the virus-receptor affinity. We propose to exploit this affinity to create a breathable virus decoy: ACE2, encapsulated inside inhalable microparticles, can be released inside the respiratory tract of the patient to bind to the virus surface before the virus reaches the target. Protein delivery to the human airways involves challenges such as toxicity of the carrier, location of deposition, and drug stability. We propose freeze spray drying, guided by computational predictions, as a solution in generating our encapsulated membrane proteins.

Covid19 has generated a global pandemic since no vaccine nor reliable clinically tested treatments are currently available. The current number of deaths is 1.5 million, and it is expected to increase. Current medical research efforts are focused on the creation of a vaccine, which is expected to be available in more than 18 months. Some attention has also been dedicated to the treatment of patients in intensive care, when the evolution of the disease has already created major damage to the lung tissue. To our knowledge, containment of the virus reproduction inside the patient, from early symptoms to critical conditions requiring intensive care, has been overlooked. A solution to this problem would reduce the probability of reaching critical conditions in the patient, and mitigate the excessive demand for medical equipment.

Growing evidence shown that ACE2 receptor is the gate for viral entry of SARS-CoV-2. To mitigate viral reproduction, current studies are trying to reduce ACE2 expression as a therapeutic principle; this is difficult to achieve, and is likely to create side effects. A better idea is to exploit the virus-receptor affinity to shield the surface of the virus before it reaches its target, so that the virus becomes inactivated. Our solution is to deliver ACE2 into the lungs of the patient with an inhaler. This strategy is challenged by the poor stability of ACE2, as well as the unknown bond strength between ACE2 and the virus in the aerodynamic environment of the lung. To deliver the payload to the lungs and ensure ACE2 stability, we will encapsulate these proteins inside breathable microparticles manufactured. To estimate the virus-receptor adhesive strength in the lung airway, we will perform multi-scale simulations based on computational molecular dynamics. The molecular design of the carrier is essential to obtain drug release at the correct location and time. We will estimate location of deposition and release time of the drug, using computational methods. To validate the efficacy of our drug, we will perform clinical tests on animals.

The success of this method will be measured by a reduction in the rate of disease development in the patient. This will potentially increment the probability of autonomous healing; hence reducing the probability of the need for intensive care. Moreover, controlling the rate of disease development with a user-friendly self-operated device will ensure the availability of hospital resources. If successful, this prototype can also be used to identify key receptors for other respiratory viruses by delivering various cell receptors into the lungs and observing the response of the patient to the drug.   

By designing an easy of use inhaler filled with encapsulated Ace2, we will be able to provide it to anyone in the world with the aim of slowing down the production rate of Covid19. The additional time before the heavy symptoms derived by Covi19 could allow to save thousands of lives. Moreover, this idea could be easily applied to any other virus affecting the airways; this would avoid future lock-downs and economical crisis.

Several full-time researchers from:

The University of British Columbia

The University of Sydney

The Woolcock Institute of Medical Research (WIMR)

Most of the experimental work in this project will be conducted at the University of British Columbia in the Faculty of Forestry and the Faculty of Land and Food Systems. A freeze drier and a spray dryer are located in the Frostad Research Group, in with Prof. Singh is a co-manager. Prof. Jiang has access to many characterization techniques, such as an atomic force microscopy and a Raman spectrometer. Moreover, Dr. Baldelli has an open access to the Bioimaging facility in which he is trained to use several types of microscopes.

Each co-investigator of this research group brings a different area of expertise required for the success of this project. Prof. Bacca will take over all the computational simulations needed to predict the adhesion between ACE2 and Covid19 and the location in which the generated microparticles will deposit in the lungs. Dr. Baldelli worked for many years with freeze and spray drying using a broad range of carriers and excipients. Prof. Carlsten is the Division Head of Respiratory Medicine and, thus, has a deep knowledge of the characteristics of ACE2. Prof. Feng and Prof. Singh are important collaborators in generating an emulsion, studies adhesion forces at the molecular level and using freeze or spray drying. Profs. Bertram, Rogak, and Bartlett are experts in aerosol generation and measurement. Prof. Traini at the University of Sydney is the director of Woolcock Institute of Medical Research and is a leading researcher in nasal and oral inhalable drug delivery.

The University of British Columbia