Published review in Spandidos Publications’ International Journal of Molecular Medicine showed Zinc possesses antiviral activity through inhibition of SARS‑CoV RNA polymerase and decreases activity of ACE2, the receptor for SARS‑CoV‑2

A review, “Zinc and respiratory tract infections: Perspectives for COVID‑19” published in Spandidos Publications’ International Journal of Molecular Medicine has shown compelling evidence that Zinc (Zn) possesses antiviral activity through inhibition of SARS‑CoV RNA polymerase. Indirect evidence also indicates that Zinc may decrease the activity of angiotensin‑converting enzyme 2 (ACE2), known to be the receptor for SARS‑CoV‑2.

These findings along with the existing data on the role of zinc in immunity raised interest to the potential use of zinc in prevention and/or treatment of common cold.

Highlights of the April 14, 2020 published review “Zinc and respiratory tract infections: Perspectives for COVID‑19“

In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS‑CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin‑converting enzyme 2 (ACE2), known to be the receptor for SARS‑CoV‑2. Improved antiviral immunity by zinc may also occur through up‑regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti‑inflammatory activity by inhibiting NF‑κB signaling and modulation of regulatory T‑cell functions that may limit the cytokine storm in COVID‑19. Improved Zn status may also reduce the risk of bacterial co‑infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID‑19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID‑19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator‑induced lung injury, modulation of antiviral and antibacterial immunity. 

Zinc was shown to have a significant impact on viral infections through modulation of viral particle entry, fusion, replication, viral protein translation and further release for a number of viruses including those involved in respiratory system pathology (37,61). Specifically, increasing intracellular Zn levels through application of Zn ionophores such as pyrithione and hinokitiol significantly alters replication of picornavirus, the leading cause of common cold (62). These findings generally correspond to the earlier indications of suppressive effect of zinc on rhinovirus replication originating from the early 1970s. 

These findings along with the existing data on the role of zinc in immunity raised interest to the potential use of zinc in prevention and/or treatment of common cold. A systematic review by Singh and Das published in Cochrane database revealed a significant reduction in common cold duration, as well as the incidence rate ratio of developing common cold (IRR=0.64 (95% CI: 0.47-0.88), P=0.006) in response to zinc supplementation. The results of meta-analysis demonstrated that Zn supplementation in the dose >75 mg/day significantly reduced duration of common colds, with Zn acetate being the most effective form

existing data clearly demonstrate that Zn ions may possess anti-inflammatory effects in pneumonia thus limiting tissue damage and systemic effects.

The obtained data demonstrate that adequate zinc status of the individual increases immune reactivity. Correspondingly, inadequate zinc supply may predispose to infectious diseases of upper and lower respiratory tract. Although the therapeutic effects of Zn are considered as inconsistent, the existing evidence-based data indicate efficiency of Zn supplementation and improvement of Zn status in prevention of pneumonia and its complications due to anti-inflammatory effect of zinc.

Certain indirect indications of the potential antiviral effect of Zn against nCoV-2019 exist, although their biomedical relevance is yet to be studied. In view of recent data on clinical course of the disease, it appears that adequate Zn status may possess protective effect as adjuvant therapy of COVID-19 through reducing lung inflammation, improvement of mucociliary clearance, prevention of ventilator-induced lung injury, modulation of antibacterial and antiviral immunity especially in elderly

Spandidos Publications, Athens Greece published review “Zinc and respiratory tract infections: Perspectives for COVID‑19”

A May 26, 2020 published paper “Can Zn Be a Critical Element in COVID-19 Treatment?” showed that SARS-CoV, HIV, HSV (herpes simplex virus), and vaccinia virus (virus used by the WHO in smallpox vaccine to trigger AIDS), are known to be inhibited by Zn salts

Zn2+ was shown to inhibit polyprotein processing in cells infected with human rhinovirus and coxsackievirus B3. In addition to SARS-CoV, a number of other viruses, including HIV, HSV (herpes simplex virus), and vaccinia virus, are known to be inhibited by Zn salts.

Zn (zinc) is known to inhibit the viral entry, blocking of polyprotein processing, or inhibition of viral RdRp activity. Using Huh7 cells transfected with in vitro synthesized capped genomic RNA of a g-1 HEV, Kaushik et al. showed that Zn but not Mg salts, namely Zn-sulfate and Zn-acetate, can inhibit viral sense and antisense RNA levels by approximately 50% at a working concentration of 10 μM. Thus, Zn salts were shown to directly inhibit the activity of viral RdRp thus inhibiting viral replication.

Zn supplement might initiate interferon (a common anti-viral agent) production by T lymphocytes. However, Zn deprivation in the lysosome of the lymphocytes triggers to secretesperforin, which also exert anti-viral activity. A pool of Zn importing inside the T lymphocytes activates T cell receptors as well as CD25 and CD69 to aid T cell proliferation and stabilization. Added Zn also contributes to the production of thymulin from the thymus and triggers T lymphocyte production. In alveolar macrophages, Zn can help to degrade the phagocytosed viral particle by the enzymes of the phagolysosome.