Interfacial Water in the SARS Spike Protein: Investigating the Interaction with Human ACE2 Receptor and In Vitro Uptake in A549 Cells

Abstract

The severity of global pandemic due to severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2) has engaged the researchers and clinicians to find the key features triggering the viral infection to lung cells. By utilizing such crucial information, researchers and scientists try to combat the spread of the virus. Here, in this work, we performed in silico analysis of the protein–protein interactions between the receptor-binding domain (RBD) of the viral spike protein and the human angiotensin-converting enzyme 2 (hACE2) receptor to highlight the key alteration that happened from SARS-CoV to SARS-CoV-2. We analyzed and compared the molecular differences between spike proteins of the two viruses using various computational approaches such as binding affinity calculations, computational alanine, and molecular dynamics simulations. The binding affinity calculations showed that SARS-CoV-2 binds a little more firmly to the hACE2 receptor than SARS-CoV. The major finding obtained from molecular dynamics simulations was that the RBD–ACE2 interface is populated with water molecules and interacts strongly with both RBD and ACE2 interfacial residues during the simulation periods. The water-mediated hydrogen bond by the bridge water molecules is crucial for stabilizing the RBD and ACE2 domains. Near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) confirmed the presence of vapor and molecular water phases in the protein–protein interfacial domain, further validating the computationally predicted interfacial water molecules. In addition, we examined the role of interfacial water molecules in virus uptake by lung cell A549 by binding and maintaining the RBD/hACE2 complex at varying temperatures using nanourchins coated with spike proteins as pseudoviruses and fluorescence-activated cell sorting (FACS) as a quantitative approach. The structural and dynamical features presented here may serve as a guide for developing new drug molecules, vaccines, or antibodies to combat the COVID-19 pandemic.

A Xanthan‐Gum‐Stabilized PEG‐Conjugated Nanocurcumin Complex: Telescoping Synthesis for Enhanced Permeation Potential

“…The À OH stretching vibration peak with higher intensity observed at around 3300 cm À 1 for CurNP (Figure 2A) indicates the role of the À OH group in intermolecular hydrogen bonding. [24] This observations were further corroborated with the density functional theory (DFT)-simulated calculation of molecular electrostatic potential values (MESP). [25] The large negative values of MESP in the range of À 50 to À 30 kcal mol À 1 (parrot ChemistryOpen green colour, Figure 3A) has been attributed to the negatively charged oxygen atoms of carbonyl and hydroxyl groups (electrophilic reactive centre).…”

“…The peak shifts of 1284 from 1273 cm −1 (Figure 2D) and of 1736 from 1718 cm −1 (Figure 2E), the strengthening of the absorption peak around 3300 cm −1 (Figure 2A), the presence of bands in the range of 2950–2850 cm −1 and 1375 cm −1 due to absorption of symmetrical as well as asymmetrical stretching vibrations of aromatic −CH 3 and −CH 2 groups and enol C−O stretching vibrations [23] indicates the interaction of RC with XG (Figures 2E and 2F) and PEG400 (Figures 2G and 2H). The −OH stretching vibration peak with higher intensity observed at around 3300 cm −1 for CurNP (Figure 2A) indicates the role of the −OH group in intermolecular hydrogen bonding [24] …”

“…The −OH stretching vibration peak with higher intensity observed at around 3300 cm −1 for CurNP (Figure 2 A) indicates the role of the −OH group in intermolecular hydrogen bonding. [24] …”

Exploring the Relationships between Structure and Antimicrobial Potency of Quinolinequinones

“…The SAR study was conducted to analyze the effect of the substituent with various positions [ 35 ]. The structures of the small library of the obtained quinolinequinones ( QQ1 – 9 ) are shown in Figure 2 .…”

On-Demand Release of Fucoidan from a Multilayered Nanofiber Patch for the Killing of Oral Squamous Cancer Cells and Promotion of Epithelial Regeneration

“…To demonstrate therapeutic results in HOK and SCC-9 cells, we quantified the cell viability of these two cell types cultured on PCM microparticles using the CCK-8 method [ 47 ]. Whether treated by irradiation or not, there was no significant difference in the HOK cell viability among the test groups.…”