Beneficial effects of HCQ and Zinc against COVID-19
The key is preventing infection and stopping post exposure viral loading through effective prophylactic treatment.
“Chloroquine interferes with a virus' ability to replicate in two ways – it alters the pH levels of the endosomes, compartments that the virus enters, and prevents the virus from plugging into the ACE2 receptors.”
1- Reduces acidity of cell walls which inhibits endocytosis, the process of viral membrane fusion to ACE2 receptors, and limits spike protein cleavage. HCQ also alters glycosylation of ACE2 and sialic acid receptors, inhibiting the virus from binding to these points.
2- HCQ is able to inhibit viral RNA replication and repackaging functions inside cells by decreasing the acidity of the cytoplasmic environment and in organelles such as the endoplasmic reticulum and the golgi apparatus which the virus uses to replicate.
3- HCQ is an effective zinc ionophore which creates passageways for Zinc to enter cells. Zinc, acting as an antiviral agent, is able to effectively block virus RDRP (RNA-dependent RNA polymerase) replication and decreases the virus’s ability to grow and be transmitted.
The complementary effect of HCQ and Zinc within the cytoplasm, through their combined MOA, inhibits every process in the replication of the virus and its ability to repackage, increase viral load and be transmitted.
4- The immunomodulatory effects of HCQ offer anti-inflammatory benefits by moderating T Cell 154 expression, BCell activation and dendritic cell activation which decreases the severity of the late stage pro-inflammatory cytokine response to the SARS-CoV-2 infection.
5- HCQ exhibits anti-thrombotic properties. It also protects ACE2 receptors which, if compromised, lead to increased levels of AT-11, causing oxidative stress, initiating the body’s pro-inflammatory cytokine response and pro-thrombotic responses in the kidneys.
Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture by Ralph S Baric in 2010.
https://pubmed.ncbi.nlm.nih.gov/21079686/
Abstract
Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV--thus eliminating the need for PT to transport Zn(2+) across the plasma membrane--we show that Zn(2+) efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn(2+) directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn(2+) was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn(2+) with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.
“There's a kinship among men who have sat by a dying fire and measured the worth of their life by it.”
Accinelli, et. al. showed that parachute level benefit was realized when HCQ was given within 72 hrs of symptom onset. The correlation between mortality and time to treatment was even tighter than between mortality and comorbidities.
https://www.sciencedirect.com/science/article/pii/S1477893921002040
Hope this helps.