Immunopharmacological perspective on zinc in SARS-CoV-2 infection

comparison with other coronaviruses such as SARS-CoV and MERS, the mortality rate of SARS-CoV-2 is lower but
the transmissibility is higher. Immune dysregulation is the most common feature of the immunopathogenesis of
COVID-19 that leads to hyperinflammation. Micronutrients such as zinc are essential for normal immune
function. According to the assessment of WHO, approximately one-third of the world’s society suffer from zinc
deficiency. Low plasma levels of zinc are associated with abnormal immune system functions such as impaired
chemotaxis of polymorphonuclear cells (PMNs) and phagocytosis, dysregulated intracellular killing, overexpression
of the inflammatory cytokines, lymphopenia, decreased antibody production, and sensitivity to microbes
especially viral respiratory infections. Zinc exerts numerous direct and indirect effects against a wide
variety of viral species particularly RNA viruses. The use of zinc and a combination of zinc-pyrithione at low
concentrations impede SARS-CoV replication in vitro. Accordingly, zinc can inhibit the elongation step of RNA
transcription. Furthermore, zinc might improve antiviral immunity by up-regulation of IFNα through JAK/STAT1
signaling pathway in leukocytes. On the other hand, zinc supplementation might ameliorate tissue damage
caused by mechanical ventilation in critical COVID-19 patients. Finally, zinc might be used in combination with
antiviral medications for the management of COVID-19 patients. In the current review article, we review and
discuss the immunobiological roles and antiviral properties as well as the therapeutic application of zinc in SARSCoV-
2 and related coronaviruses infections.