COVID-19 patients urgently need drugs that can stop the virus. So, let’s investigate how experts are working on developing and delivering drugs that may help.
In my previous article, we discussed how to get a COVID-19 vaccine. Today, we will discuss how experts deliver COVID-19 drugs. Our discussion may look similar to the previous one, but some issues may differ. Let’s discover them.
The Starting Point
COVID-19 drugs are medicines used to treat, cure, or control the COVID-19 infection. They prevent COVID-19 from spreading in the body and help our immune system clear it. Successful COVID-19 drugs are effective, safe, and selective (not harmful to our normal cells).
The following clip shows the COVID-19 infection life cycle and what the virus does in our body.
To develop drugs, experts select the best disease pathway to target. They can target; virus penetration into cells (endocytosis), virus replication in the nasal cavity, throat, and lungs, as well as transmission to other cells (exocytosis).
Researchers found that COVID-19 causes clots and complications in the major organs (lungs, hearts, livers, and kidneys). So they’ll target these areas to prevent complications. Then they’ll select the pathway to find a suitable COVID-19 drug.
Since we’re in a pandemic, experts need to get a successful COVID-19 drug as soon as possible. But, in normal situations, the journey to a successful drug may take 10-20 years.
Experts can’t wait that long. So, the first pathway is to find a licensed drug and reuse it for COVID-19. This is known as “drug repurposing.” However, since the best fit is tailored, the second pathway is to develop a targeted COVID-19 drug. Let’s discuss both pathways.
The First Pathway: Drug Repurposing
As we know, drugs must be effective, safe, and selective before being given to patients. But, the work to confirm the safety and effectiveness of drugs takes a long time, and we urgently need anti-COVID-19 drugs.
To cut down on some time required to confirm the safety and selectivity, experts propose taking known drugs and testing their effectiveness against COVID-19. Experts are working to find drug candidates. They can either:
- Test libraries of licensed drugs against COVID-19 to select the most effective candidates. This means doing an early stage of repurposing.
- Test drugs that may show activity against COVID-19, like known antiviral drugs.
- Use clinical observations.
If candidates show activity, experts can recommend to the regulatory authorities to start the late-stage of repurposing “clinical trials.“
There are several drugs that have been repurposed for COVID-19. They include:
- Chloroquine and Hydroxychloroquine: antimalarial drugs that supposedly inhibit COVID-19 fusion with body cells (endosomal acidification fusion inhibitors).
- Dexamethasone: a cortisol analog, proposed to relieve the inflammatory condition associated with COVID-19.
- Remdesivir: an antiviral drug, used previously in Ebola and Marburg virus outbreaks.
- Favipiravir: an antiviral drug, used for the flu virus.
- Lopinavir/ritonavir: anti-HIV drugs.
Experts propose that Remdesivir, Favipiravir, and Lopinavir/ritonavir drugs inhibit COVID-19 RNA replication within the body.
The Second Pathway: A Tailored Approach
As I said before, the best fit is tailored, so consider the experts’ second pathway.
- Selecting the best COVID-19 structure to target (the most druggable target) and best compound able to bind (lead compound). This is the “Discovery Stage.”
- Then, improving the lead compound properties to the optimum level. This is the “Design Stage.”
- Next, confirming the efficiency, safety, and selectivity of the design compound. This is the “Development Stage.“
In order for experts to find a lead compound, there are several sources. They include natural products, medical folklore, and previously synthesized compounds (compound libraries). For rapid screening, they may use the high-throughput and virtual screening methods.
Experts’ lead compound can bind to the target, but it may bind to other targets that causing side effects. So, they must improve its:
- Binding with the target (pharmacodynamics properties)
- Access to the target (pharmacokinetics properties)
- Safety and selectivity
Once the lead compound is optimized, it’ll be tested to ensure its efficiency, safety, selectivity, and stability. Tests may include animal and clinical trials. Here, the lead compound will be a drug candidate.
Drug clinical trials are like vaccine trials but with added patient groups in trial phases 2, 3, and 4. If the drug candidate passed the phase 3 trials, it’ll get the approval from the regulatory authorities. Meaning that it’ll reach the market as a licensed drug.
The second pathway is a long pathway, so to cut time, experts can use the fast-track strategy, computational tools, and artificial intelligence.
The drug discovery, design, and development journey is long, costly, and requires a high level of efficacy and safety. Unfortunately, it may not reach the last step. Still, the efforts of all experts are appreciated, as it is their hard work and research that will lead to finding a cure.
- BMJ Best Practice, Coronavirus disease 2019 (COVID-19)
- NIH National Center for Advancing Translation Sciences, Repurposing Drugs
- Drug repurposing: progress, challenges and recommendations
- Coronavirus puts drug repurposing on the fast track
- NIH COVID-19 Treatment Guidelines
- An Introduction to Medicinal Chemistry – fifth edition
- Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)
- Milken Institute COVID-19 Tracker
- Attrition in Drug Discovery and Development