QM/MM study of N501 involved intermolecular interaction between SARS-CoV-2 receptor binding domain and antibody of human origin.

Intermolecular interaction between key residue N501 of the epitope on SARS-CoV-2 RBD and screening antibody B38 was studied using the QM/MM and QM approach. The QM/MM optimized geometry shows that angle X-H---Y is 165° for O-H---O between mAb light chain S30 and RBD N501. High level MP2 calculations indicated the interaction between RBD N501 and S30 of B38 Fab light chain provide a relatively strong attractive force of - 3.32 kcal/mol, whereas the hydrogen bond between RBD Q498 and S30 was quantified as 0.10 kcal/mol. The decrease in ESP partial charge on hydrogen atom of hydroxyl group on S30 drops from 0.38 a.u. to 0.31 a.u., exhibiting the sharing of 0.07 a.u. from the lone pair electron oxygen of N501 due to hydrogen bond formation. The NBO occupancy of hydrogen atom also decreases from 25.79 % to 22.93 % in the hydroxyl H-O NBO bond of S30. However, the minor change of NBO hybridization of hydroxyl oxygen of S30 from sp3.00 to sp3.05 implies the rigidity of hydrogen bond tetrahedral geometry in the relative dynamic protein complex. The O-H---O angle is 165° which is close but not exactly linear. The structural requirement for sp3 hybridization of oxygen for hydroxyl group on S30 and dimension of protein likely prevent O-H---O from adopting linear geometry. The hydrogen bond strengths were also calculated using a variety of DFT methods, and the result of - 3.33 kcal/mol from the M06L method is the closest to that of the MP2 calculation. Results of this work may aid in the COVID-19 vaccine and drug screening.

A Nanomechanical Study on Deciphering the Stickiness of SARS-CoV-2 on Inanimate Surfaces.

The SARS-CoV-2 virus that causes the COVID-19 epidemic can be transmitted via respiratory droplet-contaminated surfaces or fomites, which urgently requires a fundamental understanding of intermolecular interactions of the coronavirus with various surfaces. The corona-like component of the outer surface of the SARS-CoV-2 virion, named spike protein, is a key target for the adsorption and persistence of SARS-CoV-2 on various surfaces. However, a lack of knowledge in intermolecular interactions between spike protein and different substrate surfaces has resulted in ineffective preventive measures and inaccurate information. Herein, we quantified the surface interaction and adhesion energy of SARS-CoV-2 spike protein with a series of inanimate surfaces via atomic force microscopy under a simulated respiratory droplet environment. Among four target surfaces, polystyrene was found to exhibit the strongest adhesion, followed by stainless steel (SS), gold, and glass. The environmental factors (e.g., pH and temperature) played a role in mediating the spike protein binding. According to systematic quantification on a series of inanimate surfaces, the adhesion energy of spike protein was found to be (i) 0-1 mJ/m2 for hydrophilic inorganics (e.g., silica and glass) due to the lack of hydrogen bonding, (ii) 2-9 mJ/m2 for metals (e.g., alumina, SS, and copper) due to the variation of their binding capacity, and (iii) 6-11 mJ/m2 for hydrophobic polymers (e.g., medical masks, safety glass, and nitrile gloves) due to stronger hydrophobic interactions. The quantitative analysis of the nanomechanics of spike proteins will enable a protein-surface model database for SARS-CoV-2 to help generate effective preventive strategies to tackle the epidemic.