ACE2 fragment as a decoy for novel SARS-Cov-2 virus

Fabiana Renzi; Dario Ghersi

By performing comparative structural analyses, molecular docking, and molecular dynamics simulations we identified the key residues that are involved in the binding between the viral S-protein and the human ACE2 receptor. These key residues are found in the two N-terminal back-to-back helices 1 and 2, spanning about 60 amino acids and contributing most of the predicted interaction energy between ACE2 and the SARS-Cov-2 and SARS-Cov proteins. An ideal fragment would also include the downstream betahairpin carrying the conserved Lys353. However, this residue is too far in the primary structure from the double helices. A cut and seal between these two binding regions is unlikely to work due to the unpredictable folding of the resulting chimeric structure. Therefore, we propose to use the doublehelix fragment as a candidate for effectively inhibiting the S-protein.