PMID- 35736838
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20230829
IS  - 1520-5827 (Electronic)
IS  - 0743-7463 (Linking)
VI  - 38
IP  - 26
DP  - 2022 Jul 5
TI  - Interfacial Water in the SARS Spike Protein: Investigating the Interaction with 
      Human ACE2 Receptor and In Vitro Uptake in A549 Cells.
PG  - 7976-7988
LID - 10.1021/acs.langmuir.2c00671 [doi]
AB  - 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.
FAU - Singh, Ajay Vikram
AU  - Singh AV
AUID- ORCID: 0000-0002-9875-7727
AD  - Department of Chemical and Product Safety, German Federal Institute for Risk 
      Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
FAU - Kayal, Abhijit
AU  - Kayal A
AD  - Quantumzyme LLP, Bangalore 560027, India.
FAU - Malik, Ashish
AU  - Malik A
AUID- ORCID: 0000-0002-7508-9519
AD  - Quantumzyme LLP, Bangalore 560027, India.
FAU - Maharjan, Romi Singh
AU  - Maharjan RS
AD  - Department of Chemical and Product Safety, German Federal Institute for Risk 
      Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
FAU - Dietrich, Paul
AU  - Dietrich P
AUID- ORCID: 0000-0002-2720-9918
AD  - SPECS Surface Nano Analysis GmbH, Voltastrasse 5, 13355 Berlin, Germany.
FAU - Thissen, Andreas
AU  - Thissen A
AD  - SPECS Surface Nano Analysis GmbH, Voltastrasse 5, 13355 Berlin, Germany.
FAU - Siewert, Katherina
AU  - Siewert K
AD  - Department of Chemical and Product Safety, German Federal Institute for Risk 
      Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
FAU - Curato, Caterina
AU  - Curato C
AD  - Department of Chemical and Product Safety, German Federal Institute for Risk 
      Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
FAU - Pande, Kajal
AU  - Pande K
AD  - Quantumzyme LLP, Bangalore 560027, India.
FAU - Prahlad, Dwarakanath
AU  - Prahlad D
AD  - Quantumzyme LLP, Bangalore 560027, India.
FAU - Kulkarni, Naveen
AU  - Kulkarni N
AD  - Quantumzyme LLP, Bangalore 560027, India.
FAU - Laux, Peter
AU  - Laux P
AUID- ORCID: 0000-0002-0351-3392
AD  - Department of Chemical and Product Safety, German Federal Institute for Risk 
      Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
FAU - Luch, Andreas
AU  - Luch A
AD  - Department of Chemical and Product Safety, German Federal Institute for Risk 
      Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220623
PL  - United States
TA  - Langmuir
JT  - Langmuir : the ACS journal of surfaces and colloids
JID - 9882736
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 059QF0KO0R (Water)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - A549 Cells
MH  - *Angiotensin-Converting Enzyme 2/chemistry/metabolism
MH  - *COVID-19/metabolism/virology
MH  - Humans
MH  - Molecular Dynamics Simulation
MH  - Pandemics
MH  - Peptidyl-Dipeptidase A/metabolism
MH  - Protein Binding
MH  - SARS-CoV-2/metabolism
MH  - *Spike Glycoprotein, Coronavirus/chemistry/metabolism
MH  - *Water/chemistry
EDAT- 2022/06/24 06:00
MHDA- 2022/07/08 06:00
CRDT- 2022/06/23 11:02
PHST- 2022/06/24 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2022/06/23 11:02 [entrez]
AID - 10.1021/acs.langmuir.2c00671 [doi]
PST - ppublish
SO  - Langmuir. 2022 Jul 5;38(26):7976-7988. doi: 10.1021/acs.langmuir.2c00671. Epub 
      2022 Jun 23.