Fig. 1.
Screen for potential 2019-nCoV Mpro inhibitors from commercial medicines. A: Sequence comparison between 2019-nCoV Mpro and SARS-Cov Mpro. Amino acids forming hydrogen bonds with drugs are shown in red, and their adjacent 5 amino acids on each side are shown in blue. Mutated amino acids rather than positive substitutions are shown in orange. B: Structural comparison of lopinavir/ritonavir binding pocket in SARS-CoV Mpro and 2019-nCoV Mpro. Ribbon models show the pocket structure of SARS-CoV Mpro (left) and 2019-nCoV Mpro (right), with α-helixes shown in red and β-sheets in cyan. Residues essential for lopinavir/ritonavir binding are shown in ball-and-stick format, of which Thr24, Thr26, and Asn28 are shown in purple, and Thr25, Leu27, and Asn119 are shown in blue. Protein solid surface model is shown to the right of each ribbon model, with the outer rim of the binding pocket marked by dashed yellow cycle. Mutations (marked in orange in panel A) are shown as gray balls, which are apart from the binding pocket. C: Docking model of lopinavir to 2019-nCoV Mpro. Left, overall docking model of lopinavir to 2019-nCoV Mpro; middle, enlargement of the lopinavir binding region; right, predicted chemical bonds between lopinavir and key residues of the binding pocket. D: Docking model of colistin to 2019-nCoV Mpro. Left, overall docking model of colistin to 2019-nCoV Mpro; right, predicted chemical bonds between colistin and key residues of the binding pocket. In (C) and (D), protein ribbon models are shown with the same diagram as described in (B), and drugs are shown as sticks. Hydrogen bonds between drugs and amino acids are shown as dash lines, and Pi bonds are shown as orange lines.