Virtual screening can be a helpful approach to propose treatments for COVID-19 by developing inhibitors for blocking the attachment of the virus to human cells. This study uses molecular docking, recovery time and dyn...Virtual screening can be a helpful approach to propose treatments for COVID-19 by developing inhibitors for blocking the attachment of the virus to human cells. This study uses molecular docking, recovery time and dynamics to analyze if potential inhibitors of main protease (M<sup>pro</sup>) of SARS-CoV-2 can interfere in the attachment of nanobodies, specifically Nb20, in the receptor binding domain (RBD) of SARS-CoV-2. The potential inhibitors are four compounds previously identified in a fluorescence resonance energy transfer (FRET)-based enzymatic assay for the SARS-CoV-2 M<sup>pro</sup>: Boceprevir, Calpain Inhibitor II, Calpain Inhibitor XII, and GC376. The findings reveal that Boceprevir has the higher affinity with the RBD/Nb20 complex, followed by Calpain Inhibitor XII, GC376 and Calpain Inhibitor II. The recovery time indicates that the RBD/Nb20 complex needs a relatively short time to return to what it was before the presence of the ligands. For the RMSD the Boceprevir and Calpain Inhibitor II have the shortest interaction times, while Calpain Inhibitor XII shows slightly more interaction, but with significant pose fluctuations. On the other hand, GC376 remains stably bound for a longer duration compared to the other compounds, suggesting that they can potentially interfere with the neutralization process of Nb20.展开更多
Virtual screening is a computational technique widely used for identifying small molecules which are most likely to bind to a protein target. In the present work, a molecular docking study is carried out to propose po...Virtual screening is a computational technique widely used for identifying small molecules which are most likely to bind to a protein target. In the present work, a molecular docking study is carried out to propose potential candidates for preventing the RBD/ACE2 attachment. These candidates are sixteen different flavonoids present in the peppermint leaf. Results showed that Luteolin 7-O-neohesperidoside is the peppermint flavonoid with a higher binding affinity regarding the RBD/ACE2 complex (about -9.18 Kcal/mol). On the other hand, Sakuranetin presented the lowest affinity (about -6.38 Kcal/mol). Binding affinities of the other peppermint flavonoids ranged from -6.44 Kcal/mol up to -9.05 Kcal/mol. The binding site surface analysis showed pocket-like regions on the RBD/ACE2 complex that yield several interactions (mostly hydrogen bonds) between the flavonoid and the amino acid residues of the proteins. This study can open channels for the understanding of the roles of flavonoids against COVID-19 infection.展开更多
文摘Virtual screening can be a helpful approach to propose treatments for COVID-19 by developing inhibitors for blocking the attachment of the virus to human cells. This study uses molecular docking, recovery time and dynamics to analyze if potential inhibitors of main protease (M<sup>pro</sup>) of SARS-CoV-2 can interfere in the attachment of nanobodies, specifically Nb20, in the receptor binding domain (RBD) of SARS-CoV-2. The potential inhibitors are four compounds previously identified in a fluorescence resonance energy transfer (FRET)-based enzymatic assay for the SARS-CoV-2 M<sup>pro</sup>: Boceprevir, Calpain Inhibitor II, Calpain Inhibitor XII, and GC376. The findings reveal that Boceprevir has the higher affinity with the RBD/Nb20 complex, followed by Calpain Inhibitor XII, GC376 and Calpain Inhibitor II. The recovery time indicates that the RBD/Nb20 complex needs a relatively short time to return to what it was before the presence of the ligands. For the RMSD the Boceprevir and Calpain Inhibitor II have the shortest interaction times, while Calpain Inhibitor XII shows slightly more interaction, but with significant pose fluctuations. On the other hand, GC376 remains stably bound for a longer duration compared to the other compounds, suggesting that they can potentially interfere with the neutralization process of Nb20.
文摘Virtual screening is a computational technique widely used for identifying small molecules which are most likely to bind to a protein target. In the present work, a molecular docking study is carried out to propose potential candidates for preventing the RBD/ACE2 attachment. These candidates are sixteen different flavonoids present in the peppermint leaf. Results showed that Luteolin 7-O-neohesperidoside is the peppermint flavonoid with a higher binding affinity regarding the RBD/ACE2 complex (about -9.18 Kcal/mol). On the other hand, Sakuranetin presented the lowest affinity (about -6.38 Kcal/mol). Binding affinities of the other peppermint flavonoids ranged from -6.44 Kcal/mol up to -9.05 Kcal/mol. The binding site surface analysis showed pocket-like regions on the RBD/ACE2 complex that yield several interactions (mostly hydrogen bonds) between the flavonoid and the amino acid residues of the proteins. This study can open channels for the understanding of the roles of flavonoids against COVID-19 infection.
