pH and Receptor Induced Conformational Changes-Implications Towards S1 Dissociation of SARS-CoV2 Spike Glycoprotein
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Viruses, being obligate intracellular parasites, must first attach themselves and gain entry into host cells. Viral fusion machinery is the central player in the viral attachment process in almost every viral disease. Viruses have incorporated an array of efficient fusion proteins on their surfaces to bind efficiently to host cell receptors. They make use of the host proteolytic enzymes to rearrange their surface protein(s) into the form which facilitates their binding to host-cell membrane proteins and subsequently, fusion. This stage of viral entry is very critical and has many therapeutic implications. The current global pandemic of COVID-19 has sparked severe health crisis and economic shutdowns. SARS-CoV2, the etiological agent of the disease has led to millions of deaths and brought the scientific community together in an attempt to understand the mechanisms of SARS-CoV2 pathogenesis and mortality. Like other viral fusion machinery, CoV2 spike (S) glycoprotein- ‘The Demogorgon’ poses the same questions about viral-host cell fusion. The intermediate stages of S protein-mediated viral fusion are unclear owing to the lack of structural insights and concrete biochemical evidence. The mechanism of conformational transition is still unclear. S protein binding and fusion with host cell receptors, Eg., angiotensin-converting enzyme-2 (ACE2) is accompanied by cleavage of S1/S2 subunits. To track the key events of viral-host cell fusion, we have identified ( in silico ) that low pH-induced conformational change and ACE-2 binding events promote S1 dissociation. Deciphering key mechanistic insights of SARS-CoV2 fusion will further our understanding of other class-I fusion proteins
Article activity feed
-
SciScore for 10.1101/2020.12.21.410357: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources i) pH and Charge Calculations: To observe pH-induced changes, we used PropKa 3.0 [27]. PropKasuggested: NoneThe data points were then retrieved for comprehensive plotting with GNUPLOT 5.2. GNUPLOTsuggested: (Gnuplot, RRID:SCR_008619)All these steps were performed with the Python-based tool-ProDy 1.10.11 [28]. iii) Distance Map Generation for the Receptor Bound/Unbound States: For deriving a conclusive proof for the receptor-induced conformational changes in the S1/S2 interface, we built S1/S2 distance maps for the experimental structures in closed as well as in Receptor bound states (PDB … SciScore for 10.1101/2020.12.21.410357: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources i) pH and Charge Calculations: To observe pH-induced changes, we used PropKa 3.0 [27]. PropKasuggested: NoneThe data points were then retrieved for comprehensive plotting with GNUPLOT 5.2. GNUPLOTsuggested: (Gnuplot, RRID:SCR_008619)All these steps were performed with the Python-based tool-ProDy 1.10.11 [28]. iii) Distance Map Generation for the Receptor Bound/Unbound States: For deriving a conclusive proof for the receptor-induced conformational changes in the S1/S2 interface, we built S1/S2 distance maps for the experimental structures in closed as well as in Receptor bound states (PDB ID: 6VXX and 6A98 respectively). Python-basedsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 21. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
-
