The current COVID-19 pandemic caused by SARS-CoV-2 has prompted investigators worldwide to search for an effective anti-viral treatment. A number of anti-viral drugs such as ribavirin, remdesivir, lopinavir/ritonavir, antibiotics such as azithromycin and doxycycline, and anti-parasite such as ivermectin have been recommended for COVID-19 treatment. In addition, sufficient pre-clinical rationale and evidence have been presented to use chloroquine for the treatment of COVID-19. Furthermore, Zn has the ability to enhance innate and adaptive immunity in the course of a viral infection. Besides, Zn supplement can favour COVID-19 treatment using those suggested and/or recommended drugs. Again, the effectiveness of Zn can be enhanced by using chloroquine as an ionophore while Zn inside the infected cell can stop SARS-CoV-2 replication. Given those benefits, this perspective paper describes how and why Zn could be given due consideration as a complement to the prescribed treatment of COVID-19.
Why Is Zn Critical for COVID-19 Treatment?
Zn Can Enhance Cell-Mediated and Adaptive Immunity in the Course of Infection Zinc is thoroughly involved in cell-mediated immunity against any infectious agent such as bacteria and virus. Zinc is one of the major factors that control function and proliferation of neutrophils, NK cells, macrophages, and T and B lymphocytes as well as cytokine production by the immune cells. Zn also mediates protection from the adverse effect of ROS that are generally produced during inflammatory processes. Free intracellular Zn2+ is essential in extravasation to the site of the infection and uptake and killing of microorganisms by neutrophils.
Augmented Effect of Zn and Chloroquine to Stop SARS-CoV-2 Replication Chloroquine was known to increase vacuolar pH when trapped in acidic organelles, such as lysosomes. This increase in pH disrupts lysosomal acidification leading to the impairment of autophagosome fusion and autophagic degradation [90, 91]. Using human ovarian carcinoma cell line A2780, Xue J. et al.  reported that chloroquine can act as ionophore for Zn. Chloroquine enhances uptake of Zn by the lysosomes, and the combination of Zn and chloroquine enhances chloroquine cytotoxicity and induces apoptosis in malignant cells. In their experiment , A2780 ovarian cancer cells were treated with 100–300 μM chloroquine in the presence of increased concentrations of ZnCl2 for 1 h. Intracellular basal Zn levels were barely detectable in control cells without any chloroquine. However, chloroquine addition to the culture medium caused significant increases of intracellular Zn in a dose-dependent manner.
Zn Can Directly Inhibit SARS-CoV-2 Replication Using recombinant SARS-CoV nsp12, te Velthuis et al.  showed that Zn2+ directly inhibited the in vitro RdRp activity (Fig. 1). They also reported that specifically, Zn2+ was found to inhibit the SARS-CoV RdRp elongation and template binding. Earlier, it was also shown that Zn2+ inhibited the proteolytic processing of replicase polyproteins
Zinc plays crucial roles in many aspects of life. In the course of infection, the immunomodulatory role of Zn is well evident. In the current pandemic of SARS-CoV-2, Zn supplement could play an important role to treat COVID-19 patients such as (i) added immune boosting effects with anti-viral drugs and (ii) stopping SARS-CoV-2 replication in infected cells, if combined with chloroquine. In view of this discussion, oral Zn supplement can be given using a suitable form of Zn-salt.
Reference & source information: https://link.springer.com/
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