“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.

MacKenzie&Greeff