Computationally engineered ACE2 decoy binds with nanomolar affinity with the SARS-CoV-2 spike protein

Abstract

Even with the availability of vaccines, therapeutic options for COVID-19 still remain highly desirable, especially in hospitalized patients with moderate or severe disease. Soluble ACE2 (sACE2) is a promising therapeutic candidate that neutralizes SARS CoV-2 infection by acting as a decoy. By using computational mutagenesis, we designed a number of sACE2 derivatives carrying 3 to 4 mutations. The top predicted sACE2 decoy based upon the in silico mutagenesis scan was subjected to molecular dynamics and free energy calculations for further validation.