Novel ACE2-Fc Decoy for Treatment of SARS-CoV-2

COVID-19 virus invades human cells via host ACE2 receptor, and strategies aimed at disrupting this process are being explored. These include monoclonal antibodies that target viral Spike, or S protein, that engages human ACE2 receptor. A number of monoclonal antibodies are in late stage clinical trials and have shown antiviral efficacy. However, there are two major concerns about therapeutic antibodies: 1. The virus is constantly evolving, and new mutations may ultimately evade existing antibody drugs; 2. Antibodies do not safeguard readiness for future pandemics. To circumvent these shortcomings of therapeutic antibodies, initiatives in building an ACE2 decoy drug have started. These alternatives take into consideration that despite of acquiring new mutations, COVID-19 invariably needs to engage ACE2 as their gateway to human cells, and therefore an ACE2 decoy can always trap the mutating virus. Furthermore, ACE2 is even shared among distantly related coronaviruses including SARS in the 2003 outbreak and the current COVID-19, suggesting a successfully constructed and validated antiviral based on an ACE2-trap may be broadly effective against future coronaviruses. My lab has been working on ACE2 and ACE2-based drugs for years and the current proposal focuses on a new design with additional features to boost its antiviral efficacy.