The CoviD-19 Saga: Finding a Cure

Part 1

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Drugs take time to develop. Historically, drugs were discovered by identifying the active ingredient of traditional remedies or by accidental discovery, such was the case of penicillin.

Modern drug discoveries involve a multitude of processes from screening hits which involve identifying molecules with the desired type of activity in an assay and it takes a lot medical chemistry and pharmacology. This efforts make sure the drug or the drug’s active ingredient will have an increased affinity to its desired effect, becomes much more selective to reduce all potential side effects, increase its efficacy, potency, metabolic stability, bioavailability; it’s a mouthful. Once this (drug discovery) efforts prove successful the next step is drug development which leads to clinical trials.

And clinical trials take an average of 6-8 years to finish, maybe even longer before it becomes publicly available in the market. All of the drugs you see in the pharmacy are a product of such rigorous screening and each year new drugs that have finished their clinical trial run surface and become available to the public. This creation process and length is generally the same for vaccines.

This is why it’s not that easy to search for a cure. The enemy must be studied for a weakness before a spear is thrust into it, but this weapon must be of balance and precision, or else it will backfire. Various diseases from previous outbreaks continue to provide us with new insight through research, even years after it has happened. Most of their treatment options remain in development. That’s how long it takes to find a cure. What more when the enemy is novel and new?

CoviD-19 Drug Development

The sudden appearance of a novel coronavirus shocked the globe. As it quickly turned into a pandemic, studies and research about the disease move around the clock as we speak, and the health sector together with global authorities scramble to contain it while a definite treatment is being synthesized. It has no known treatment (yet) and most of the recovered cases relied on their own immune systems with the help of supportive treatments and experimental drugs.

More than 200 drug companies, biotech firms, University research groups and various health organizations pooled in efforts to fast-track work and researches for a cure, with 115 vaccine candidates and 129 potential therapies in various stages of pre-clinical or clinical drug development.

A global coalition is formed which aims to facilitate rapid reviews of clinical trial proposals by ethics committees and national regulatory agencies, fast-track approvals for the candidate therapeutic compounds, ensure standardized and rapid analysis of emerging efficacy and safety data, and facilitate sharing of clinical trial outcomes before publication.

By March 2020, the International Coalition for Epidemic Preparedness Innovations (CEPI) committed to research investments worth US$100 million across several countries, and issued an urgent call to raise and rapidly invest $2 billion for vaccine development.

Various groups including the Bill and Melinda Gates foundation together with partners invested US$125 million and coordinated with WHO to fast track development of potential treatments.

The process of drug discovery for an antiviral compound has started for SARS CoV-2. While this would definitely take years, another process called drug repurposing / repositioning is happening. It uses numerous established antiviral compounds for treating other infections to be repurposed or developed in new clinical research efforts to alleviate the growing threat as soon as possible.

Drug Repurposing / Repositioning

This process involves the investigation of existing drugs for new therapeutic purposes. Drug repositioning has been widely used to reduce the number of required clinical trial steps. It aims as well to reduce time and costs for a treatment candidate to reach the market. It leads to possible discovery of combination treatment that was previously unknown, and facilitate the discovery of new mechanism of action for old drugs.

The downside is that the dosage required for the treatment of a novel disease usually differs from that of its original target disease, and this means, most of the time, the researchers would have to begin from Phase 1 which relative to drug discovery would lead to the same time frame. Patient rights and legal issues are also possible drawbacks.

Repurposed Drugs that are currently under Phase III-IV trials include Hydroxychloriquine / Chloriquine, Remdesivir, Favipiravir, Lopinavir, Sarilumab, and Tocilizumab.

Hydroxychloriquine / Chloriquine

Chloroquine is an antimalarial medication that is also used against auto-immune diseases such as rheumatoid arthritis and Lupus erythematosus. The drug became a potential treatment candidate because of previous studies dated October 2004, a group of researchers at the Rega Institute for Medical Research published a report on chloroquine, stating that it acts as an effective inhibitor of the replication of SARS-CoV in vitro so it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2.

On March 18, 2020, the WHO announced that chloroquine and the related hydroxychloroquine would be among the four drugs studied as part of the Solidarity clinical trial (the others were remdesivir, lopinavir + ritonavir combination and lopinavir + ritonavir + interferon-beta combination).

Chloroquine has a relatively narrow therapeutic index and it can be toxic at levels not much higher than those used for treatment—which raises the risk of inadvertent overdose. It is also contraindicated for people with heart disease or diabetes due to its several side effects. A study of chloroquine in 81 hospitalized people in Brazil was halted. About 40 people with coronavirus got 600 milligram doses over 10 days. By the sixth day of treatment, 11 of them had died, leading to an immediate end to the high-dose segment of the trial.

There is a fair warning from health experts against the misuse of non-pharmaceutical versions of chloroquine phosphate (or any other drug for that matter). I think it is best that our authorities and our media should be careful in endorsing drugs to the public, as miscommunication can prove fatal. A husband and wife from Arizona consumed a fish tank antiparasitic containing chloroquine phosphate on 24 March, 2020 with the intention of it being prophylaxis against COVID-19. One of them died and the other was hospitalized.

We will continue to discuss repurposed drugs on The Covid-19 saga: Finding a Cure part 2 (link) And while you are here, let us again to remind you that our battle with this pandemic has just started. And as we continue to brace ourselves and find a cure for this disease, may we also look for cures of a society long ill that helped sprung forth this calamity. Stay Safe.

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