The magnified infectious power of the SARS–CoV–2 virus compared to its precursor SARS–CoV is intimately linked to an enhanced ability in the mutated virus to find available hydrogen bond sites in the host cells. This characteristic is acquired during virus evolution because of the selective pressure exerted at the molecular level. We pinpoint the specific residue (in the virus) to residue (in the cell) contacts during the initial recognition and binding and show that the virus· · · cell interaction is mainly due to an extensive network of hydrogen bonds and to a large surface of non–covalent interactions. In addition to the formal quantum characterization of bonding interactions, computation of absorption spectra for the specific virus· · · cell interacting residues yields significant shifts of ∆λ max = 47 and 66 nm in the wavelength for maximum absorption in the complex with respect to the isolated host and virus, respectively.
Descriptors of chemical bonding derived from five different
analysis
tools based on quantum mechanics (natural charges, electron density
differences, atoms in molecules (AIM), natural bond orbitals (NBO),
and non-covalent interactions (NCI) index) consistently afford a picture
of a wall of weak, non-covalent intermolecular interactions separating
anionic Ibuprofen from the environment. This wall, arising from the
cumulative effect of a multitude of individual weak charge transfer
interactions to the interstitial region between fragments, stabilizes
the drug at all equilibrium positions in the free energy profile for
its insertion into model cell membranes. The formal charge in anionic
Ibuprofen strengthens all intermolecular interactions, having a particularly
strong effect in the network of water to water hydrogen bonds in the
solvent. Electron redistribution during the insertion process leads
to a sensible reduction of electron delocalization in both the CO2
– group and the aromatic ring of Ibuprofen.
Here, we conclusively show that, despite their purely classical origin,
randomly chosen configurations from molecular dynamics simulations
provide deep insight into the purely quantum nature of bonding interactions.
Notwithstanding the very weak nature of individual contacts, it is the cumulative effect of a large number of interactions (green NCI surfaces) which provides macroscopic stability to the interfaces.
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