“our results identify ZAP as an effector of the IFN response against SARS-CoV-2, although this pandemic pathogen may be preadapted to the low CpG [dinucleotide] environment in humans.”
And no, it doesn’t mean taking lots of zinc will cure COVID. biorxiv.org/content/10.110…
And no, it doesn’t mean taking lots of zinc will cure COVID. biorxiv.org/content/10.110…
Not CpG dinucleotides (5'—C—phosphate—G—3' , that is, cytosine and guanine separated by only one phosphate group) are used in regulation of gene expression by methylation of the cytosine.
CpG sites are underrepresented in the human genome.
en.m.wikipedia.org/wiki/CpG_site
CpG sites are underrepresented in the human genome.
en.m.wikipedia.org/wiki/CpG_site
*Note (not not).
To investigate selection pressures on HCovVs they determined CpG frequencies and distribution in human and animal CoVs. They found that CpG dinucleotides are generally suppressed and observed a trend towards lower CpG frequencies in hCoVs compared to their non-human CoVs.
“SARS-CoV-2 showed stronger CpG suppression than SARS-CoV and MERS-CoV, albeit with substantial variation across its genome. Remarkably, the closest bat relatives of SARS-CoV-2 display the strongest CpG suppression of all coronaviruses available from this natural reservoir host.”
“we found that the CpG targeting host factor ZAP is expressed in human lung cells and restricts SARS-CoV-2 especially in the presence of [interferons beta, gamma and lambda].”
“Our data suggest that zoonotic transmission of a coronavirus with an unusually low frequency of CpG dinucleotides facilitated the pandemic spread of SARS-CoV-2 although it does not confer full resistance to ZAP-mediated restriction.”
One wild idea (just me putting 2 and 2 together and getting ~22) is Toll-like Receptor 9 (TLR9) is involved in detecting CpG to fight extracellular pathogens (amongst many things in humans) and is elevated in PBMC during SARS-CoV-2 infection.
bmcinfectdis.biomedcentral.com/articles/10.11…
bmcinfectdis.biomedcentral.com/articles/10.11…
“the possibility that SARS-CoV-2 originated from a zoonotic virus showing a particularly low frequency of CpG dinucleotides.
“the two closest animal relatives of SARS-CoV-2 (RaTG13 and RmYN02) show markedly lower CpG frequencies than all remaining 180 [sequenced] bat viruses”
“the two closest animal relatives of SARS-CoV-2 (RaTG13 and RmYN02) show markedly lower CpG frequencies than all remaining 180 [sequenced] bat viruses”
“a small insertion that is present in SARS-CoV-2 Spike but not in its relatives from bats and pangolins not only introduced a potential furin cleavage site but also an additional clustered CpG motif that may be targeted by ZAP“
“SARS-CoV-2 may already have been preadapted to the low CpG environment in humans because it’s closest known counterparts from bats contains an unusually low frequency of CpG dinucleotides.”
