Computational investigation on the antioxidant activities and on the Mpro SARS-CoV-2 non-covalent inhibition of isorhamnetin

Abstract

In the present work, we report a computational study on some important chemical properties of the flavonoid isorhamnetin, used in traditional medicine in many countries. In the course of the study we determined the acid-base equilibria in aqueous solution, the possible reaction pathways with the •OOH radical and the corresponding kinetic constants, the complexing capacity of copper ions, and the reduction of these complexes by reducing agents such as superoxide and ascorbic anion by using density functional level of theory Density Functional Theory. Finally, the non-covalent inhibition ability of the SARS-CoV-2 main protease enzyme by isorhamnetin was examined by molecular dynamics (MD) and docking investigation.

Primary Antioxidant Power and Mpro SARS‐CoV‐2 Non‐Covalent Inhibition Capabilities of Miquelianin

“…The comparison in Table 4, with systems studied previously and using a similar computational protocols, reveals that, in a lipid-like environment, the antioxidant activity of miquelianin (8.91×10 0 M À 1 s À 1 ) is lower than scutellarein (1.06×10 3 ), [29] isorhamnetin (2.53×10 1 ) [28] and quercetin (4.39×10 3 M À 1 s À 1 ), [34] and higher than that of scutellarin (3.57×10 À 6 M À 1 s À 1 ). [30] The same comparison in water solution shows that Miq has an antioxidant power against the * OOH radical, slightly lower than that of isorhamnetin [28] and quercetin, [34] but higher than that of scutellarin, [30] scutellarein, [29] daphnetin. [35] With respect to Trolox, [36] which is generally used as a reference, miquelianin is more active by about four orders of magnitude (see Table 4).…”

“…The computations have been performed in the framework of Quantum Mechanicsbased Test for Overall Free Radical Scavenging Activity (QM-ORSA) methodology, successfully employed in other similar studies. [28][29][30][31] Furthermore, the non-covalent inhibition power of the SARS-CoV-2 main protease enzyme (M pro ) of miquelianin species present at physiological pH (7.4), has been tested by using docking tools and molecular dynamics applying a computational protocol previously employed for other quercetin-like antioxidants. [28] Ongoing research in this area can enable the development of new antiviral molecules helpful to combat future pandemics.…”

“…[28][29][30][31] Furthermore, the non-covalent inhibition power of the SARS-CoV-2 main protease enzyme (M pro ) of miquelianin species present at physiological pH (7.4), has been tested by using docking tools and molecular dynamics applying a computational protocol previously employed for other quercetin-like antioxidants. [28] Ongoing research in this area can enable the development of new antiviral molecules helpful to combat future pandemics. Indeed, computational modeling represents an effective strategy for the separation and quantification of the atomistic and molecular sources that contribute to the biologically relevant events, providing details that can support experimental findings or inspire new approaches.…”

Theoretical Insights into the Oxidative Stress-Relieving Properties of Pinocembrin─An Isolated Flavonoid from Honey and Propolis

“…Despite the compound having only two hydroxyl groups, neutral and monoanionic species are anticipated to coexist in water at a pH of 7.4. This is due to two factors: (1) deprotonation of C 7 often occurs before reaching physiological pH; 22,24,38,53 (2), C 5 −OH, which can participate in an intramolecular hydrogen bond with an adjacent carbonyl oxygen, indirectly contributes to density delocalization, thereby stabilizing the system and reducing the tendency for dissociation. 31 The initial dissociation indeed takes place at C 7 , which has a pK a1 value of 7.40.…”

“…One such mechanism is chelation of transition metals (type II activity), typically copper and iron, that partake in the Fenton reaction, leading to the formation of hydroxyl radicals. Such metal binding generally impedes interaction with O 2 •– in redox processes, as confirmed by reaction rate constants . The third approach to action (type III) centers on preventing the formation of free radicals in vivo through blocking enzymes responsible for their generation during catalytic activity.…”