Journal
PATHOGENS
Volume 10, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/pathogens10060669
Keywords
coronavirus; influenza virus; S; E; HA; M2; S-acylation; palmitoylation; DHHC; pandemic preparedness
Categories
Funding
- DFG [Ve 141/18-1]
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Recent pandemics caused by zoonotic coronaviruses and influenza A viruses have shown that viral glycoproteins and ion channels are S-acylated. DHHC family members play a crucial role in palmitoylation, with a common set of DHHCs acylating SARS-CoV-2 and Flu A proteins in human cells. This highlights the potential of DHHCs as targets for broad-spectrum antiviral drugs.
Recent pandemics of zoonotic origin were caused by members of coronavirus (CoV) and influenza A (Flu A) viruses. Their glycoproteins (S in CoV, HA in Flu A) and ion channels (E in CoV, M2 in Flu A) are S-acylated. We show that viruses of all genera and from all hosts contain clusters of acylated cysteines in HA, S and E, consistent with the essential function of the modification. In contrast, some Flu viruses lost the acylated cysteine in M2 during evolution, suggesting that it does not affect viral fitness. Members of the DHHC family catalyze palmitoylation. Twenty-three DHHCs exist in humans, but the number varies between vertebrates. SARS-CoV-2 and Flu A proteins are acylated by an overlapping set of DHHCs in human cells. We show that these DHHC genes also exist in other virus hosts. Localization of amino acid substitutions in the 3D structure of DHHCs provided no evidence that their activity or substrate specificity is disturbed. We speculate that newly emerged CoVs or Flu viruses also depend on S-acylation for replication and will use the human DHHCs for that purpose. This feature makes these DHHCs attractive targets for pan-antiviral drugs.
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