Hydroxychloroquine, Chloroquine and Zinc – Revisited

FDA Research

The FDA is sponsoring ongoing human drug trials each with a rigorous research methodology to test the efficacy, recommended dosage, and possible toxicity of chloroquine. These studies do take time to conduct, analyze, and report. We are likely many weeks, if not months, away from the results and recommendations.

The Analog of Tamiflu

Tamiflu is an influenza antiviral medication. If taken early in the infection, Tamiflu disrupts the flu virus’ replication process, lowers the viral load in the body, and reduces the severity and duration of a patient’s illness. Tamiflu must be taken early in a patient’s illness to have a significant beneficial effect.

The same would be true of chloroquine with zinc, if it functions as some believe (but not yet confirmed). Therein is the rub.

Remember, some of those infected with the coronavirus are asymptomatic. They may not even know they are ill. Still others suffer only mild symptoms and may confuse their illness with some other malady. Those with more severe infections often wait days before seeking medical intervention, there are further delays in obtaining test results (if you can obtain a test), and finally hospitalization. By the time a sick person is seen by hospital staff, they may have long passed the point where this drug therapy can produce a significant outcome. In other words, the best outcomes—again, if this therapy works as believed by some—are achieved by taking the therapy as early as possible in the course of the illness.

Finally, chloroquine, like any drug, present some toxicities. People with diabetes, certain coronary issues (e.g., hypertension), retinal issues (e.g., macular degeneration), and other underlying medical issues are at risk. Yet, they are often the most ill in hospital care for this disease and for whom hope is especially reserved.

A Critical Detour:

Chloroquine is a form of zinc ionophore (here) that increases a virus cell’s ability to accept the attachment of zinc. Zinc disrupts (here) the ability of a viral pathogen to adversely affect otherwise healthy human cells. This is why some members of the research community believe that chloroquine with zinc shows promise in treating the coronavirus.

Do not miss this important point: Chloroquine’s, sole role in proposed treatment of the coronavirus is to serve a facilitating role. That role is to bind zinc to viral cells.  It’s the zinc which impedes the replication of the corona virus—not the chloroquine: “In this instance, chloroquine has no drug action. It is the zinc that is in play, and I find it concerning that so many news organizations (and governments) are failing to convey this fact..opting, instead, to portray chloroquine as having the key drug action” (here).

Zinc is like a hitch hiker. Chloroquine is like the driver stopping to offer a ride. Every hitch hiker prioritizes a ride to their preferred destination. In this case, the destination are the cells of the viral pathogen, COVID-19.

Current Drug Trials in the Literature

There are four drug trials (as of this date) in the literature. Two, out of China, show chloroquine are ineffective treatment strategies for the coronavirus. A third trial lacked a control group—a critical component in any drug trial.

Medcram does report on a fourth test at six minutes and forty-four seconds into its video. The narrator is scrupulous to point out at the time the video was produced the only information about the trial conducted by a well-regarded researcher in the south of France is what the newspaper reported. The newspaper reported apparent therapeutic value in administering chloroquine to a small sample of twenty coronavirus patients.

Subsequent to the video’s production, this drug trial was peer reviewed by other researchers. The study’s research methodology was characterized as a “hot mess.” The results were not too surprisingly called into question.

The Best of Scientific Research and Thought Today

Let’s hope that there is an existing drug therapy produced for another purpose which can be used to treat the coronavirus. However, rigorous drug trials are a prerequisite to establish efficacy, dosage levels, and possible toxicity.

A visitor to my blog pointed me to a web site, Medcram (here), that does an excellent job explaining not only the biology of the coronavirus but also the epidemiological issues in its transmission. I invite you to visit the site, and in this regard, to follow the updates (here and here) offered about the possible use of chloroquine with zinc.

Next, a brief detour (tl;dr):

Pharmaceutical companies seek to develop drug therapies and some of their therapeutic candidates start with an understanding of human cell biology. Their theories are based on the best peer juried research conducted throughout the research community. But here’s the thing about research, in general. What cell biologists are thinking today is based on the best past and current research findings of which they are aware. Future research may produce (additional) confirmation, or something less than that. So, scientists are VERY careful to note what they and others believe to be the best in informed thinking. As lay readers (i.e., me and probably you), we may miss their careful wording about the limits of what is hard fact and what is (perhaps) the best informed conjecture.

Drug therapies are expensive to produce. The best scientific thinking may lead to promising drug candidates constructed on only the best of scientific research and wisdom at the time. That’s why some drug candidates that look good in the lab fail in animal testing. That’s why some drug candidates that show continued promise in animal testing fail in human trials. This is a very challenging process with far more losers than winners.

The same is true for possible repurposing of existing drug therapies—developed for another purpose altogether—when applied to a current topic of research, like the coronavirus.

At six minutes and ten seconds into an update on the possible use of chloroquine in the treatment of the coronavirus, the narrator discusses how the virus transfers genetic material into a human cell and how the revised cell replicates. How the virus transfers its genetic sequence is the issue here. The latest research suggests how this process (might) work. However, the narrator is careful to state that we do not know for certain if this is what is actually taking place. BUT IF IT IS, then he describes how the zinc in combination with chloroquine COULD disrupt the transfer process.

Stop. Another detour:

Pharmacological and medical researchers trained in their fields’ research methodologies understand what their peers sometimes (and somewhat unfairly) call “weasel words” or “hedging” (here). Science doesn’t always know a thing as a fact. Science research is based on what is known as a dialectic (here) that, over time, renders previously suspected things to be incorrect only to be replaced by newer suspected things based on more recent research and scholarship.

Today, the cell biologists and virologists have a working theory on how genetic material is transferred from one cell to another—in this case, coronavirus RNA into an otherwise healthy human cell’s RNA. Current theory may be correct. It may be partially correct. It may even be incorrect.

If current thought is accurate, chloroquine may play a critical part in disrupting the transfer and offer therapeutic value in treating the coronavirus. That’s what peer juried drug trials are designed to (dis)confirm.

Copyright 2020, Howard D. Weiner