Intracellular elemental zinc (Zn) inhibits various RNA viruses including coronaviruses.2 In a 2010 study, Zn coupled with an Zn ionophore (pyrithione), showed potent inhibition of SARS‐CoV replication (even at very low micromolar concentrations). Zn directly inhibited the coronaviral RNA‐dependent RNA polymerase, which functions as the core enzyme of the RNA viral synthesizing machinery.2 Zn also inhibits SARS‐CoV papain‐like protease 2, which is also a key enzyme for viral replication and assembly of functional viral proteins.3 Zn and several Zn chelates were shown to inhibit furin (proprotein convertase) which is important in the pathogenesis of many viruses.4 The furin proteases have been proposed as therapeutic targets for several viral pathogens.5 Specifically, the spike glycoprotein of SARS‐CoV‐2 contains a unique furin cleavage site that is not found in SARS‐CoV.6 This furin activation mechanism increases the infectivity and pathogenicity of viruses.6 Zn inhibition of host furin in SARS‐CoV‐2 infection may be an important antiviral mechanism unique to this novel strain.
Chloroquine has been shown to be a potent Zn ionophore and transports Zn through the cell membrane substantially increasing intracellular levels of Zn, especially in the endosomal‐lysosomal compartment.7 These same ionophore properties presumably apply to the closely related molecule, hydroxychloroquine (HCQ).
— Read on onlinelibrary.wiley.com/doi/10.1002/jmv.26523
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