Molecular dynamics simulations of aqueous systems of inhibitor candidates for adenosine-5’-phosphosufate reductase

Silva, Talis Uelisson da; Pougy, Karina de Carvalho; Albuquerque, Magaly Girão; Lima, Camilo Henrique da Silva; Machado, Sérgio de Paula

doi:10.1080/07391102.2022.2033137

Cited by 4 publications

(1 citation statement)

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“…Molecular dynamics (MD) simulations were carried out using GROMACS 2018.1 package 21 with CHARMM36 force field 43 from the best pose obtained by molecular docking. In addition, the enzyme topology preparation, calculation, and results analysis were carried out according to our group's description 17 , 44 , 45 . Each enzyme-ligand complex was inserted and centered in a periodic triclinic box (box dimensions: 3.982 × 4.337 × 5.086 nm; box volume: 702.68 nm 3 ), solvated with water TIP3P type and then neutralized with sufficient positive (Na + ) or negative (Cl - ) ions.…”

Section: Methodsmentioning

confidence: 99%

Molecular modelling studies and in vitro enzymatic assays identified A 4-(nitrobenzyl)guanidine derivative as inhibitor of SARS-CoV-2 Mpro

de Santiago-Silva,

Camargo,

Carvalho Constant

et al. 2024

Sci Rep

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Scientists and researchers have been searching for drugs targeting the main protease (Mpro) of SARS-CoV-2, which is crucial for virus replication. This study employed a virtual screening based on molecular docking to identify benzoylguanidines from an in-house chemical library that can inhibit Mpro on the active site and three allosteric sites. Molecular docking was performed on the LaSMMed Chemical Library using 88 benzoylguanidine compounds. Based on their RMSD values and conserved pose, three potential inhibitors (BZG1, BZG2, and BZG3) were selected. These results indicate that BZG1 and BZG3 may bind to the active site, while BZG2 may bind to allosteric sites. Molecular dynamics data suggest that BZG2 selectively targets allosteric site 3. In vitro tests were performed to measure the proteolytic activity of rMpro. The tests showed that BZG2 has uncompetitive inhibitory activity, with an IC50 value of 77 µM. These findings suggest that benzoylguanidines possess potential as Mpro inhibitors and pave the way towards combating SARS-Cov-2 effectively.

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