Abstract
Non-structural accessory proteins in viruses play a key role in hijacking the basic cellular mechanisms, which is essential to promote the virus survival and evasion of the immune system. The immonuglobulin-like open reading frame 8 (ORF8) protein expressed by SARS-CoV-2 accumulates in the nucleus and may influence the regulation of the gene expression in infected cells. In this contribution, by using micro-second time-scale all-atom molecular dynamics simulations, we unravel the structural bases behind the epigenetic action of ORF8. In particular, we highlight how the protein is able to form stable aggregates with DNA through a histone tail-like motif, and how this interaction is influenced by post-translational modifications, such as acetylation and methylation, which are known epigenetic markers in histones. Our work not only clarifies the molecular mechanisms behind the perturbation of the epigenetic regulation caused by the viral infection, but also offers an unusual perspective which may foster the development of original antivirals.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
† Electronic Supplementary Information (ESI) available: Time series of the RMSD for all the systems, time series of the crucial distances between ARKS and the closest nucleotides, binding free energies between ORF8 and DNA also in presence of acetylation/methylation of K36.