Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture.
Level 5 - mechanism / opinion, no new human data
In vitro cell culture and cell-free biochemical assay (bench research)
PubMed 21079686 · doi:10.1371/journal.ppat.1001176
What was done
Researchers evaluated the effect of combining Zn(2+) with the zinc ionophore pyrithione (PT) on the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. They also assessed the direct effect of Zn(2+) on viral RNA synthesis using replication and transcription complexes (RTCs) isolated from infected cells and cell-free enzymatic assays with purified recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) from E. coli, testing reversibility using the chelator MgEDTA.
What was found
The combination of 2 µM Zn(2+) and 2 µM PT inhibited the replication of both SARS-CoV and EAV in cell culture. In cell-free assays, Zn(2+) directly inhibited RdRp activity in both viruses: it blocked the initiation step of EAV RNA synthesis, whereas it inhibited elongation and reduced template binding for SARS-CoV RdRp. The inhibition was reversed by chelating Zn(2+) with MgEDTA. Quantitative percentage inhibition and IC50 values were not reported in the abstract.
Why it matters
The study identifies a direct molecular mechanism showing that elevated intracellular zinc impedes nidovirus RNA-dependent RNA polymerases. This establishes a biochemical basis for exploring zinc ionophores and RdRp inhibition in coronavirus research.
Limits
This work is restricted entirely to cell culture and cell-free biochemical assays; no animal models or human subjects were evaluated. Viral replication inhibition in intact cells required an ionophore (pyrithione) to transport zinc across the plasma membrane, so findings cannot be directly translated to dietary zinc supplementation or clinical treatment.
Cited by
- partial Zinc inhibits the activity of RNA-dependent RNA polymerase, thereby inhibiting the replication of RNA viruses.