Structure of SARS-CoV-2 main protease in the apo state

High-resolution mining of the SARS-CoV-2 main protease conformational space: supercomputer-driven unsupervised adaptive sampling

“…If the protomer 1 is clearly not evolving over the simulation, protomer 2 evolves slowly towards the discussed 2 states organization. Overall, our results are compatible with the description of the Zhou et al apo crystal structure 49 who observed a incomplete structured oxyanion hole exhibiting several mixed states of structuring. This highlights the large flexibility of the enzyme discussed in the experimental Literature at room temperature.…”

“…These results demonstrate that the oxyanion hole is only partially organized in the other protomer. It is consistent with experimental data on the apo state 49 and also with the data on the active protomer of the holo state which shows distances around 5 Å (see reference 37 and references herein for a discussion of the different available crystal structures).…”

“…Recently, Zhou et al published an experimental study of the apo structure (PDB 1UJ1) 49 at physiological pH. They found several features allowing for the characterization of the presence of the oxyanion hole structure which is a key structural element of the activity of each protomer.…”

“…Concerning the apo state, recent experimental results lead to a potential low activity of the apo dimer in link with an observed destructured oxyanion hole. 49 It is important to point out that distances/markers exhibit a distribution of different values centered around a maximum of frequency due to the liquid conditions that differ from the crystal ones.…”

Identification of the Potential Hits for Hindering Interaction of SARS-CoV-2 Main Protease (M pro ) from the Pool of Antiviral Phytochemicals utilizing Molecular Docking and Molecular Dynamics (MD) Simulations

“…has shown covalent bonding in Computer-Aided Drug Design (CADD) analysis with M pro . The compound efficiently destroys the virus in in vivo experiments, but clinical findings have not yet been identified which lead to the inclusion of natural alternatives such as phytochemicals as a target against M pro [21].…”