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

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 sp...

Ausführliche Beschreibung

Bibliographische Detailangaben
Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1999. - 38(2022), 26 vom: 05. Juli, Seite 7976-7988
1. Verfasser: Singh, Ajay Vikram (VerfasserIn)
Weitere Verfasser: Kayal, Abhijit, Malik, Ashish, Maharjan, Romi Singh, Dietrich, Paul, Thissen, Andreas, Siewert, Katherina, Curato, Caterina, Pande, Kajal, Prahlad, Dwarakanath, Kulkarni, Naveen, Laux, Peter, Luch, Andreas
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Spike Glycoprotein, Coronavirus spike protein, SARS-CoV-2 Water 059QF0KO0R Peptidyl-Dipeptidase A EC 3.4.15.1 ACE2 protein, human EC 3.4.17.23 Angiotensin-Converting Enzyme 2
LEADER 01000naa a22002652 4500
001 NLM342579657
003 DE-627
005 20231226014436.0
007 cr uuu---uuuuu
008 231226s2022 xx |||||o 00| ||eng c
024 7 |a 10.1021/acs.langmuir.2c00671  |2 doi 
028 5 2 |a pubmed24n1141.xml 
035 |a (DE-627)NLM342579657 
035 |a (NLM)35736838 
040 |a DE-627  |b ger  |c DE-627  |e rakwb 
041 |a eng 
100 1 |a Singh, Ajay Vikram  |e verfasserin  |4 aut 
245 1 0 |a Interfacial Water in the SARS Spike Protein  |b Investigating the Interaction with Human ACE2 Receptor and In Vitro Uptake in A549 Cells 
264 1 |c 2022 
336 |a Text  |b txt  |2 rdacontent 
337 |a ƒaComputermedien  |b c  |2 rdamedia 
338 |a ƒa Online-Ressource  |b cr  |2 rdacarrier 
500 |a Date Completed 07.07.2022 
500 |a Date Revised 29.08.2023 
500 |a published: Print-Electronic 
500 |a Citation Status MEDLINE 
520 |a 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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Spike Glycoprotein, Coronavirus  |2 NLM 
650 7 |a spike protein, SARS-CoV-2  |2 NLM 
650 7 |a Water  |2 NLM 
650 7 |a 059QF0KO0R  |2 NLM 
650 7 |a Peptidyl-Dipeptidase A  |2 NLM 
650 7 |a EC 3.4.15.1  |2 NLM 
650 7 |a ACE2 protein, human  |2 NLM 
650 7 |a EC 3.4.17.23  |2 NLM 
650 7 |a Angiotensin-Converting Enzyme 2  |2 NLM 
650 7 |a EC 3.4.17.23  |2 NLM 
700 1 |a Kayal, Abhijit  |e verfasserin  |4 aut 
700 1 |a Malik, Ashish  |e verfasserin  |4 aut 
700 1 |a Maharjan, Romi Singh  |e verfasserin  |4 aut 
700 1 |a Dietrich, Paul  |e verfasserin  |4 aut 
700 1 |a Thissen, Andreas  |e verfasserin  |4 aut 
700 1 |a Siewert, Katherina  |e verfasserin  |4 aut 
700 1 |a Curato, Caterina  |e verfasserin  |4 aut 
700 1 |a Pande, Kajal  |e verfasserin  |4 aut 
700 1 |a Prahlad, Dwarakanath  |e verfasserin  |4 aut 
700 1 |a Kulkarni, Naveen  |e verfasserin  |4 aut 
700 1 |a Laux, Peter  |e verfasserin  |4 aut 
700 1 |a Luch, Andreas  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Langmuir : the ACS journal of surfaces and colloids  |d 1999  |g 38(2022), 26 vom: 05. Juli, Seite 7976-7988  |w (DE-627)NLM098181009  |x 1520-5827  |7 nnns 
773 1 8 |g volume:38  |g year:2022  |g number:26  |g day:05  |g month:07  |g pages:7976-7988 
856 4 0 |u http://dx.doi.org/10.1021/acs.langmuir.2c00671  |3 Volltext 
912 |a GBV_USEFLAG_A 
912 |a SYSFLAG_A 
912 |a GBV_NLM 
912 |a GBV_ILN_22 
912 |a GBV_ILN_350 
912 |a GBV_ILN_721 
951 |a AR 
952 |d 38  |j 2022  |e 26  |b 05  |c 07  |h 7976-7988