COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now claimed 1,076 lives in Malaysia, and 288,229 persons have been confirmed infected. 

These figures continue to rise, challenging every effort to contain and break the chain of infection through mass movement control. The first vaccine from Pfizer-BioNTech has just arrived, and along with other vaccines yet to arrive, provide a ray of hope to achieve herd immunity. But that takes time and there are lots of unknown. 

Given the rapid spread of SARS-CoV-2 and the high morbidity and mortality caused by the infection, it is imperative for health authorities to leverage on treatments that are already available and have established efficacy and safety – high-dose ascorbate (vitamin C) and Ivermectin, as an adjunct treatment to the Covid-19 immunisation programme. 

In research for an efficacious medication, it is not enough to show the cause and effect. The mechanism of how the treatment agent works has to be well explained. Both ascorbate and Ivermectin as therapeutic agents for Covid-19 have shown therapeutic effects in clinical studies and in practice. Besides, their mechanisms of action have been ascertained. 

It has now been established that the Angiotensin-Converting Enzyme II receptor (ACE2) is the entry point by which coronaviruses can infect body cells. Li et al (2003) and Hoffman et al (2005) first postulated that ACE2 was a functional receptor for SARS coronavirus cellular entry. SARS-CoV-2 shares this route of entry and has been confirmed (Lan et al, 2020; Yan et al, 2020; and Zhou et al, 2020) after the Covid-19 outbreak at end or 2019. 

Understanding the SARS-CoV-2 cell entry mechanism is crucial and also informs intervention strategies. 

ACE2, an integral membrane protein, is present in many types of cells, and especially more in the pulmonary, cardiovascular, gastrointestinal, and renal systems. As such, the coronaviruses are able to enter the cells over a large part of the body, particularly affecting the lungs and the inner lining of the blood vessels causing microscopic blood clots.

In healthy individuals, the ACE2 levels are considerably low. Ingraham et al (2020) postulated that chronically elevated levels of ACE2 are independent predictors of disease progression. 

Informed by prior studies on the effectiveness of ascorbate – against H1N1 (Jariwalla et al, 2007); bird flu H5N1 (Dervabin et al, 2008); avian flu H9N2 in vitro and in vivo (Barbour et al, 2009); and HIV (Jariwalla et al, 2010); my associates in the Dr Rath Research Institute in California investigated the efficacy of micronutrients in suppressing the cellular expression of ACE2 receptors in lung epithelial and vascular endothelial cells.   

The study of Ivanov et al (2020) showed that a micronutrient composition comprising ascorbate was able to suppress coronavirus entry into the body in both normal and inflammatory conditions. In another study by Ivanov, Goc, Ivanova et al (2020) published in Infectious Diseases: Research and Treatment, it was shown that ascorbate alone and in combination with other natural compounds could lower ACE2 expression at the cellular, protein, and RNA levels; hence, giving implication for their beneficial therapeutic use against Covid-19. 

During the peak of the Covid-19 infection in China in early 2020, Chinese scientists conducted three clinical trials using high-dose intravenous vitamin C to positive results. Those experimental studies showed cause and effect without explaining the mechanism how it worked against coronavirus. The results of Ivanov and colleagues’ studies helped close this gap.

Invermectin, a drug that was originally approved for veterinary and has since repurposed for humans and now sporadically used in clinics for Covid-19 infection with reported success. The US National Institutes of Health has now dropped its recommendation against this inexpensive antiparasitic drug for treatment of Covid-19. It neither advises nor is against its use, leaving the decision to physicians and their patients. 

A systematic review and meta-analysis of 27 studies evaluating Ivermectin for prophylaxis and treatment of Covid-19 (Lawrie, 2020) showed the drug to reduce morbidity and mortality from Covid-19 infection. It also concluded that Ivermectin should be openly used.

Like ascorbate, the mechanism of action against coronavirus has also been established. The coronavirus, upon entry to human cells, binds to a receptor, toll-like receptor 4 (TLR4), and triggers two internal mechanisms to activate production of cytokines that cause inflammation. Ivermectin binds to the TLR4 receptor to prevent viral attachment and inflammation. 

Ivermectin also inhibits importins, the intracellular transport proteins used by viruses to enter the nucleus and replicate their genetic materials, hence having an effect on Covid-19. 

The therapeutic effect of both ascorbate and ivermectin is based on controlling the ACE2 expression and also disrupting the replication cycle of the virus. These mechanisms of action will also work on newer strains arising from the mutated SARS-CoV-2.  

There is equipoise, or reasonable bioethics for the use of ascorbate and Ivermectin as adjunct treatment against Covid-19. We have nothing to lose. – February 25, 2021.

* Captain Dr Wong Ang Peng is a researcher with an interest in economics, politics, and health issues. He has a burning desire to do anything within his means to promote national harmony. Captain Wong is also a member of the National Patriots Association.

* This is the opinion of the writer or publication and does not necessarily represent the views of The Malaysian Insight. Article may be edited for brevity and clarity.