Hijacking of Cellular Functions by Severe Acute Respiratory Syndrome Coronavirus-2. Permeabilization and Polarization of the Host Lipid Membrane by Viroporins.
J Phys Chem Lett
; 13(21): 4642-4649, 2022 Jun 02.
Article
in English
| MEDLINE | ID: covidwho-1860273
ABSTRACT
Like all viral infections, SARS-CoV-2 acts at multiple levels, hijacking fundamental cellular functions and assuring its replication and immune system evasion. In particular, the viral 3' Open Reading Frame (ORF3a) codes for a hydrophobic protein, which embeds in the cellular membrane, where it acts as an ion viroporin and is related to strong inflammatory response. Here we report equilibrium and enhanced sampling molecular dynamic simulation of the SARS-CoV-2 ORF3a in a model lipid bilayer, showing how the protein permeabilizes the lipid membrane, via the formation of a water channel, which in turn assures ion transport. We report the free energy profile for both K+ and Cl- transfer from the cytosol to the extracellular domain. The important role of ORF3a in the viral cycle and its high conservation among coronaviruses may also make it a target of choice for future antiviral development, further justifying the elucidation of its mechanism at the atomistic level.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cell Membrane
/
Viroporin Proteins
/
COVID-19
Limits:
Humans
Language:
English
Journal:
J Phys Chem Lett
Year:
2022
Document Type:
Article
Affiliation country:
Acs.jpclett.2c01102
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