How zinc supplementation prevents Viral replication in covid-19 patients

Covid-19 is a systemic disease that affects the lungs and multiple organs and tissues. It is transmitted, rapidly from one person to another in close proximity, through contact with virus laden aerosols discharged in coughs and sneezes. Most affected patients die as a result of acute respiratory distress syndrome.

There are several variants of Covid-19, but the Alpha, Delta, and Omicron variants are most widely spread with severe health breakdown.

 

Symptoms Of Covid-19

The symptoms of covid-19 are similar to those of normal cold and flu. They are:

  • High temperature or chills
  • Continuous cough
  • Change in the sense of smell and taste
  • Short breath
  • Feeling of tiredness
  • Headache and body pains

 

Viral Life Cycle And Cell Invasion Of Covid-19

Once the virus gained entrance into the host body, it binds to host receptors and enters the host cells through endocytosis or membrane fusion. The virus is made up of for structural proteins, which are the,

  • Spike (S) protein
  • Membrane (M) protein
  • Envelope (E) protein
  • Nucleocapsid (N) protein

The S protein protrudes from the viral surface and is the most important viral protein for host attachment and penetration. It is composed of two functional subunits (S1 and S2). The S1 is responsible for viral binding to the host cell receptor, angiotensin-converting enzyme 2 (ACE-2) and the S2 subunit plays a role in the fusion of viral and host cellular membranes.

 

Corona Virus Undergoes Two-step Protease Cleavage After Activation

After binding to the ACE-2, the S protein undergoes activation through a two-step protease cleavage. The first cleavage is for priming at the S1/S2 cleavage site. The second cleavage activation occurs at a position adjacent to a fusion peptide within S2 subunit. Thus, the initial cleavage is for stabilization of S2 subunit while the second cleavage is activates the S protein and causes a conformational change that leads to viral and host cell membrane fusion.

Once the virus has gained entrance into the host cell, it undergoes viral replication and formation of a negative strand RNA by the pre-existing single-stranded positive RNA through RNA polymerase activity. The negative stranded RNA newly formed starts to produce new strands of positive RNAs, which then synthesize new proteins in the cytoplasm.

The viral N protein now binds the new genomic RNA and the M protein facilitates its integration to the cellular endoplasmic reticulum (ER). The newly formed nucleocapsids are then enclosed in the ER membrane and transported to the lumen. From the lumen, it is transported through Golgi vesicles to the cell membrane and then, through exocytosis to the extracellular space. The new viral particles are now ready to infect the next epithelia cell.

 

How Does Zinc Protect The Body From Entering Of The Virus?

When an individual is infected with coronavirus, the virus first targets the epithelium and ciliary dyskinesia for damage, thereby impairing mucocilia clearance. But zinc supplementation increases ciliary beat frequencies and thereby improves ciliary clearance of viral particles. The improved ciliary clearance also reduces bacterial infection.

 

How Does Zinc Directly Inhibit Viral Replication?

At first, zinc prevents viral fusion with the host membrane, decreases the viral polymerase functions, impairs the protein translation and processing and blocks viral particle release. It also destabilizes the viral envelope. When supplemented with a small concentration of the zinc ionophores pyrithione or hinokitol, zinc decreases viral RNA synthesis by directly inhibiting the RNA-dependent RNA polymerase of the virus.

 

REFERENCES

Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients. (2017) 9:1286. doi: 10.3390/nu9121286

Gammoh NZ, Rink L. Zinc in infection and inflammation. Nutrients. (2017) 9:624. doi: 10.20944/preprints201705.0176.v1

Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; in press.