Proposed model of the Dictyostelium cAMP receptors bound to cAMP

Greenhalgh, Jack; Chandran, Aneesh; Harper, Matthew T.; Ladds, Graham; Rahman, Taufiq

doi:10.1016/j.jmgm.2020.107662

Cited by 6 publications

(1 citation statement)

References 51 publications

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“…Before performing any docking with the ZINCPharmer-derived hits, validation docking was performed with known inhibitor X77. The latter was blindly docked [69,70] against the entire SARS-CoV-2 M pro structure using AutoDock Vina [22]. The highest-ranked (i.e., with the lowest predicted free energy of interaction, ∆G, kcal/mol) docked pose of X77 was superimposed on its original pose present in the crystal structure, and the RMSD was calculated in DockRMSD v1.1 [71].…”

Section: Molecular Dockingmentioning

confidence: 99%

Novel Small-Molecule Scaffolds as Candidates against the SARS Coronavirus 2 Main Protease: A Fragment-Guided in Silico Approach

et al. 2020

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The ongoing pandemic caused by the novel coronavirus has been the greatest global health crisis since the Spanish flu pandemic of 1918. Thus far, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 1 million deaths, and there is no cure or vaccine to date. The recently solved crystal structure of the SARS-CoV-2 main protease has been a major focus for drug-discovery efforts. Here, we present a fragment-guided approach using ZINCPharmer, where 17 active fragments known to bind to the catalytic centre of the SARS-CoV-2 main protease (SARS-CoV-2 Mpro) were used as pharmacophore queries to search the ZINC databases of natural compounds and natural derivatives. This search yielded 134 hits that were then subjected to multiple rounds of in silico analyses, including blind and focused docking against the 3D structure of the main protease. We scrutinised the poses, scores, and protein–ligand interactions of 15 hits and selected 7. The scaffolds of the seven hits were structurally distinct from known inhibitor scaffolds, thus indicating scaffold novelty. Our work presents several novel scaffolds as potential candidates for experimental validation against SARS-CoV-2 Mpro.

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