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10.1128/JVI.00426-20 http://scihub22266oqcxt.onion/10.1128/JVI.00426-20 32295925!7307142!32295925     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Virol 2020 ; 94 (13): ä Nephropedia Template TP {{tp|p=32295925|t=2020. Ca(2+) Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity |pdf=|usr=}}{{32295925}} gab.com Text Ca(2+) Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity JO: J Virol http://www.kidney.de/pget.php?&tw=1&pmid=32295925 #FOAvip Fusion with, and subsequent entry into, the host cell is one of the critical steps in the life cycle of enveloped viruses. For Middle East respiratory syndrome coronavirus (MERS-CoV), the spike (S) protein is the main determinant of viral entry. Proteolytic cleavage of the S protein exposes its fusion peptide (FP), which initiates the process of membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium ions (Ca(2+)) play an important role in fusogenic activity via a Ca(2+) binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FPs share a high sequence homology, and here, we investigated whether Ca(2+) is required for MERS-CoV fusion by screening a mutant array in which E and D residues in the MERS-CoV FP were substituted with neutrally charged alanines (A). Upon verifying mutant cell surface expression and proteolytic cleavage, we tested their ability to mediate pseudoparticle (PP) infection of host cells in modulating Ca(2+) environments. Our results demonstrate that intracellular Ca(2+) enhances MERS-CoV wild-type (WT) PP infection by approximately 2-fold and that E891 is a crucial residue for Ca(2+) interaction. Subsequent electron spin resonance (ESR) experiments revealed that this enhancement could be attributed to Ca(2+) increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry showed an approximate 1:1 MERS-CoV FP to Ca(2+) ratio, as opposed to an 1:2 SARS-CoV FP to Ca(2+) ratio, suggesting significant differences in FP Ca(2+) interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging infectious disease with zoonotic potential and has reservoirs in dromedary camels and bats. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans, with 2,468 confirmed cases causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. In order to develop novel drugs and vaccines, it is important to understand the molecular mechanisms that enable the virus to infect host cells. Our data have found that calcium is an important regulator of viral fusion by interacting with negatively charged residues in the MERS-CoV FP region. This information can guide therapeutic solutions to block this calcium interaction and also repurpose already approved drugs for this use for a fast response to MERS-CoV outbreaks. Twit Text FOAVip Ca(2+) Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity ????J Virol http://www.kidney.de/pget.php?&tw=1&pmid=32295925 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32295925 #FOAvip English Wikipedia <ref>{{Cite pmid|32295925}}</ref> Ca(2+) Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity #MMPMID32295925 Straus MR; Tang T; Lai AL; Flegel A; Bidon M; Freed JH; Daniel S; Whittaker GR J Virol 2020[Jun]; 94 (13): ä PMID32295925show ga Fusion with, and subsequent entry into, the host cell is one of the critical steps in the life cycle of enveloped viruses. For Middle East respiratory syndrome coronavirus (MERS-CoV), the spike (S) protein is the main determinant of viral entry. Proteolytic cleavage of the S protein exposes its fusion peptide (FP), which initiates the process of membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium ions (Ca(2+)) play an important role in fusogenic activity via a Ca(2+) binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FPs share a high sequence homology, and here, we investigated whether Ca(2+) is required for MERS-CoV fusion by screening a mutant array in which E and D residues in the MERS-CoV FP were substituted with neutrally charged alanines (A). Upon verifying mutant cell surface expression and proteolytic cleavage, we tested their ability to mediate pseudoparticle (PP) infection of host cells in modulating Ca(2+) environments. Our results demonstrate that intracellular Ca(2+) enhances MERS-CoV wild-type (WT) PP infection by approximately 2-fold and that E891 is a crucial residue for Ca(2+) interaction. Subsequent electron spin resonance (ESR) experiments revealed that this enhancement could be attributed to Ca(2+) increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry showed an approximate 1:1 MERS-CoV FP to Ca(2+) ratio, as opposed to an 1:2 SARS-CoV FP to Ca(2+) ratio, suggesting significant differences in FP Ca(2+) interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging infectious disease with zoonotic potential and has reservoirs in dromedary camels and bats. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans, with 2,468 confirmed cases causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. In order to develop novel drugs and vaccines, it is important to understand the molecular mechanisms that enable the virus to infect host cells. Our data have found that calcium is an important regulator of viral fusion by interacting with negatively charged residues in the MERS-CoV FP region. This information can guide therapeutic solutions to block this calcium interaction and also repurpose already approved drugs for this use for a fast response to MERS-CoV outbreaks. |*Host-Pathogen Interactions[MESH] |*Membrane Fusion[MESH] |*Virus Internalization[MESH] |Amino Acid Sequence[MESH] |Amino Acid Substitution[MESH] |Animals[MESH] |Calcium/*metabolism[MESH] |Cell Line[MESH] |Chlorocebus aethiops[MESH] |Coronavirus Infections/*metabolism/*virology[MESH] |Humans[MESH] |Ions/*metabolism[MESH] |Middle East Respiratory Syndrome Coronavirus/pathogenicity/*physiology[MESH] |Models, Molecular[MESH] |Mutation[MESH] |Protein Binding[MESH] |Proteolysis[MESH] |Spike Glycoprotein, Coronavirus/chemistry/genetics/metabolism[MESH] |Structure-Activity Relationship[MESH] |Vero Cells[MESH] |Virulence[MESH]Ca(2+) Ions Promote Fusion of Middle East Respiratory Syndrome Coronav(epmc).pdf DeepDyve Pubget Overpricing