Currently, there are no approved vaccines or pharmaceutical therapies available for prevention of SARS- CoV-2 infection or treatment of COVID-19. The development of a specific vaccine is not expected for at least 12-18 months due to required time for research, evaluation, and regulatory approval. So the 'repurposing' of available and approved drugs has emerged as a feasible strategy for treatment near term. In this regard, potentially suitable antiviral and immuno modulatory candidates have been identified and realized.

Covid-19 Drug Therapy options. Clinical drug/drug information Solutions

https://www.elsevier.com/data/assets/pdf_file/0007/988648/COVID-19-Drug-Therapy_Mar-2020).

Here's an insight to the most potent immune-competent element that's been discussed in all current forums, the 'Zinc': its absorbable forms (Zinc citrate) and role in curbing the Covid-19menace.

Zinc is an essential trace element that has a critical role in maintaining structural and catalytic functions of >200 enzymes involved in major metabolic pathways, including nucleic acid metabolism, protein synthesis, and cell division (Br J Nutr. 2008;99(Suppl 3): S14-23). Although it remains difficult to define zinc status, zinc deficiency appears to be negatively affecting immune competence increasing morbidity and mortality (Food Nutr Bull. 2004; 25:S99-S203). The WHO considers zinc deficiency to be a major contributor to the burden of disease in developing countries especially in those with a high mortality rate (TheWorldHealthReport2002: reducing risks, promoting healthy lives. Geneva: World Health Organization; 2002), which is apparently relevant in the present scenario of COVID -19.

The role of zinc as an antiviral can be separated into two categories:

1. Zinc supplementation to improve antiviral response and systemic immunity

2. Zinc treatment performed to specifically inhibit virus replication or infection related symptoms So, what does Zinc do specifically in the immune responses?

Zn2+inhibits the corona virus RNA polymerase activity and blocks the replication of the virus inside cells.

(PLoS Pathog 6(11): e 1001176.doi10.1371/journal.ppat.1001176)

Studies show that when more quantities of Zinc were administered in the cells, less viral RNA was produced. So zinc actually could block viral reproduction.

(https://journals.plos.org/plosone.article?id=10.137/jounal.pone.0109180)

Next Question is does enough ions penetrate the block the viral reproduction?

The Answer is 'No'!! That means we need a high concentration of Zinc out side

The cells and would need to Zinc 'lonophores' to transport them to the site of action.

An interesting finding demonstrated that Chloroquine has characteristics of a zinc ionosphere and specifically targets the extracellular trace element zinc to intracellular lysosomes.

(PLoS One 2014;9:e109180. doi: 10.1371/journal.pone.0109180. eCollection 2014).

Chloroquine (CQ) and Hydroxy chloroquine (HCQ) act as weak bases and accumulate within endosomes, lysosomes, or Golgi vesicles within cells resulting in increase of pH (Int J Antimicrob Agents 2007;30(4):297-308). As coronavirus requires acidification of endosomes for proper functioning

(Int J Biol Sci 2020;16(10):1724-31. doi:10.7150/ijbs.45498), a pH increase in intracellular compartments is a wise strategy in the treatment of SARS-CoV-2. It is hypothesized that effective zinc supplementation during treatment of COVID-19 with CQ and HCQ, which have zinc ionophore characteristics, may result in increased intracellular zinc levels in general and in lysosomes specifically. Higher intracellular zinc levels might result in a more efficient RdRp (RNA dependant RNA polymerase) inhibition and consequently a more effective inhibition of intracellular SARS-CoV- 2 replication, potentially improving clinical outcomes of hospitalized COVID-19 patients treated with CQ or HCQ

( doi: 10.20944/preprints202004.0124.v1).

The zinc compound with promising absorption properties is zinc citrate which has a high zinc content of 31% and has very good sensory properties as well. Studies indicate that zinc citrate is effective in the prevention of zinc deficiency (doi:10.3945/jn.113.181487) and presumably also in the treatment of COVID -19 as it traverses its path from bench to bedside.