Computational analysis of substrate recognition of Sars-Cov-2 Mpro main protease.

M main protease takes an essential role in the Sars-Cov-2 viral life cycle by releasing the individual protein from the single poly-peptide chain via proteolytic cleavage in the beginning of the viral infection. Interfering with this step by inhibiting the protease with small compound-based inhibitors has been proven to be an effective strategy to treat the infection. Thus, understanding the substrate recognition mechanism of the M main protease has gained great interest from the beginning of the pandemic. Here, we have studied the substrate recognition mechanism of the protease by means of the molecular dynamic methods. We have found that the glutamine residue at P1 has paramount effect in the interaction with the substrates as expected. In addition, we also have shown that for the first time, the arginine amino acid at the P3-P5 along with P4' can strengthen the interaction.