Autophagy and evasion of immune system by SARS-CoV-2. Structural features of the Non-structural protein 6 from Wild Type and Omicron viral strains interacting with a model lipid bilayer. †
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Abstract
The viral cycle of SARS-CoV-2 is based on a complex interplay with the cellular machinery, which is mediated by specific proteins eluding or hijacking the cellular defense mechanisms. Among the complex pathways called by the viral infection autophagy is particularly crucial and is strongly influenced by the action of the non-structural protein 6 (Nsp6) interacting with the endoplasmic reticulum membrane. Importantly, differently from other non-structural proteins Nsp6 is mutated in the recently emerged Omicron variant, suggesting a possible different role of autophagy. In this contribution we explore, for the first time, the structural property of Nsp6 thanks to long-time scale molecular dynamic simulations and machine learning analysis, identifying the interaction patterns with the lipid membrane. We also show how the mutation brought by the Omicron variant may indeed modify some of the specific interactions, and more particularly help anchoring the viral protein to the lipid bilayer interface.
Analysis protein of the secondary structure and of the specific lipid/amino acid interactions. RMSF per amino acid. Distribution of the distance between the center of mass of the 89 to 99 α-helix and the center of the lipid bilayer. Analysis of the behavior of the 195 to 207 α-helix. See DOI: 10.1039/x0xx00000x
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SciScore for 10.1101/2022.01.05.475107: (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 52 The lipid and the protein have been represented by the Amber ff1453,54 force field while water has been modeled via TIP3P.55 MD simulations have been performed using the NAMD code,56,57 using periodic boundary condition (PBC) and the constant number of particle, pressure, and temperature (NPT) ensemble, using a Langevin thermostat and barostat.58,59 A time step of 4fs has been used to integrate the Newton equation of motion thanks to the use of Hydrogen Mass Repartition (HMR)60 in combination with RATTLE and SHAKE. Ambersuggested: (AMBER, RRID:SCR_016151)NAMDsuggested: (NAMD, RRID:SCR_01…SciScore for 10.1101/2022.01.05.475107: (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 52 The lipid and the protein have been represented by the Amber ff1453,54 force field while water has been modeled via TIP3P.55 MD simulations have been performed using the NAMD code,56,57 using periodic boundary condition (PBC) and the constant number of particle, pressure, and temperature (NPT) ensemble, using a Langevin thermostat and barostat.58,59 A time step of 4fs has been used to integrate the Newton equation of motion thanks to the use of Hydrogen Mass Repartition (HMR)60 in combination with RATTLE and SHAKE. Ambersuggested: (AMBER, RRID:SCR_016151)NAMDsuggested: (NAMD, RRID:SCR_014894)Results 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 11. 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.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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