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Editor, Senior Moderator
Biochem Biophys Res Commun. 2020 Feb 17. pii: S0006-291X(20)30339-9. doi: 10.1016/j.bbrc.2020.02.071. [Epub ahead of print] [h=1]Structure analysis of the receptor binding of 2019-nCoV.[/h]
Chen Y[SUP]1[/SUP], Guo Y[SUP]1[/SUP], Pan Y[SUP]2[/SUP], Zhao ZJ[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.
Copyright ? 2020 The Authors. Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Coronavirus; Molecular modeling; Sequence analysis; Structure analysis
PMID: 32081428 DOI: 10.1016/j.bbrc.2020.02.071
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Chen Y[SUP]1[/SUP], Guo Y[SUP]1[/SUP], Pan Y[SUP]2[/SUP], Zhao ZJ[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.
Copyright ? 2020 The Authors. Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Coronavirus; Molecular modeling; Sequence analysis; Structure analysis
PMID: 32081428 DOI: 10.1016/j.bbrc.2020.02.071
Free full text