Inhibition of the main protease of SARS-CoV-2 (Mpro) by repurposing/designing drug-like substances and utilizing nature’s toolbox of bioactive compounds

Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT

“…Another relevant aspect to highlight from these results is that the hydration obtained for the mM pro ( 0.57) is equal to the value reported for lysozyme ( 0.57) and close to porcine elastase ( 0.53) using other proteases models ( Fornés, 2008 ). In fact, this degree of hydration is high and any change in this can significantly affect the molecular recognition events for this protease, since it is known that for this type of biochemical reaction in proteins, hydration is an extremely important driving force ( Chalikian, 2021 ). It is very important to note there are no reports of this type of data for proteases associated with SARS-CoV-2 and in particular for M pro .…”

“…As some authors ( Alvarado et al, 2018 , Alvarado et al, 2015 , Alvarado et al, 2021 ) have conclusively demonstrated, this type of study provides information on the role played by hydration in modulating protein stability and its role in ligand binding reactions. It is important to mention that it has been shown that protein-protein and protein-ligand interactions occur with the loss or gain of water molecules around the ligand and/or protein (biological water), a phenomenon with potential pharmacological impact because it is key to the biological activity of these proteins ( Antonopoulou et al, 2022 , Awoonor-Williams and Abu-Saleh, 2021 , Azam et al, 2021 , Azam et al, 2020 , Ball, 2017 , Barletta and Fernández-Alberti, 2018 , Barletta et al, 2019 , Blake and Soliman, 2014 , Brovchenko et al, 2010 ). Despite the theoretical effort made and the in vitro studies of its antiviral activity to date, there are still no experimental reports that confirm the binding and perturbation of M pro by ivermectin.…”

Drug repurposing against main protease and RNA-dependent RNA polymerase of SARS-CoV-2 using molecular docking, MM-GBSA calculations and molecular dynamics

“…Non-covalent inhibition depends on hydrogen binding, and hydrophobic and ionic interactions to create a reversible interaction with the active site that may or may not involve the conserved catalytic residue Cys145 [ 54 ]. However, it is necessary to establish an interaction with one or more of the main interactive residues: Glu166, His41, Gly143, Ser144 and Cys145 [ 39 ]. As observed in Glide docking, the reference, natamycin and denufosol interacted with Glu 166 through hydrogen binding, while the final contact between nadide and Glu 166 was observed during molecular dynamic simulation.…”

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

“…Taking into consideration all the above, and the fact that there are numerous natural compounds that are being screened for their antiviral properties and have exhibited efficacy in fighting a wide range of viruses, including SARS-CoV-2, plants emerge as a potential valuable source of bioactive compounds, which could be utilized as nutraceuticals to contribute to the protection against a viral infection and potentially aid immunity [ 16 , 17 , 18 ].…”