The chance for a breakthrough: Can Chloroquine fight off Covid-19?
In the time of pandemic and global panic, there is only one thing that can make everyone feel better. These are the words “We’ve found the cure.” So far, there is no established medicine for Covid-19. Scientists all over the world strive to slow down the spread of the virus, and medical specialists try to alleviate the symptoms of those who were infected. Some pharmaceutical companies have engaged in the development of the vaccine for the Covid-19, but clinical trials and development process can take more than a year and require significant financial input.
However, scientists have shown that Chloroquine, a medicine designed for malaria treatment, has potential efficacy against SARS-CoV-2, aetiological agent of COVID-19. Sounds incredible, right? Before you get too excited, take your time and learn if there is any hope for the cure.
What is so dangerous about Covid-19?
The term “Coronavirus” covers a similar group of viruses that may cause diseases in mammals and birds. In humans, these viruses cause respiratory infections, varying from mild ones such as common cold to more dangerous, including SARS, MERS, and COVID-19. The SARS-CoV-2 virus, also known as COVID-19, emerged in December 2019 in China and despite drastic measures, keeps spreading rapidly all over the world. The good thing is that the coronavirus mortality rate doesn’t exceed 2%, which is much below other well-known diseases.
COVID-19 may transfer from one person to another, even when the symptoms are not present. Common ones include:
- Cough
- High temperature
- Shortness of breath
These symptoms remind of common cold or flu and do not necessarily mean you have caught the virus. In the most severe cases, COVID-19 leads to acute respiratory failure.
COVID-19 is thought to spread from human to human via airborne droplets and is highly unlikely to be spread through parcels or food. Usually, the incubation period of the coronavirus lasts from 2 to 14 days, but according to the latest findings may remain detectable up to 37 days.
What measures are already taken?
On March 12, UK Chief Medical Officers raised the status of coronavirus risk in the UK from moderate to high. Some time earlier, the UK government has developed the coronavirus action plan and announced strengthened legal powers to protect public health. Moreover, the Health Protection (Coronavirus) Regulations 2020 have been established to reduce the risk of further human-to-human coronavirus spread in the UK. The Regulation includes self-isolation if public health professionals assume that an individual may have the virus.
Medical specialists all around the world recommend the following precautionary measures:
- Using various antiviral drugs that may cause an only indirect effect on SARS-CoV-2
- Stimulating the immune system, e.g. with the use of steroids
- Maintaining the functioning of the body organs, e.g. with the use of lung ventilation equipment and manipulations with kidneys
Global institutions, including the UK National Health Service (NHS), suggests that personal hygiene may reduce risks of catching the virus and recommend to do the following:
- Wash hands with soap and water and use hand sanitisers;
- Use a tissue or sleeve when coughing or sneezing;
- Avoid close contact with infected people or those who feel unwell;
- Avoid touching nose, eyes, or mouth with dirty hands;
- Wear a mask only if you’ve got the virus or work as a healthcare professional in high-risk environments.
In case someone is infected, has visited a high-risk country or there’s a possible risk of coronavirus, he will be asked to self-isolate and avoid contact with people for 14 days.
The places with a high risk of coronavirus include Cambodia, China, Hong Kong, Iran, Italy, Japan, Laos, Macau, Malaysia, Myanmar (Burma), Singapore, Taiwan, Tenerife — only the H10 Costa Adeje Palace Hotel, South Korea, Thailand, and Vietnam.
UK residents can obtain medical help or medical advice via NHS 111 — an online coronavirus service. If the symptoms worsen during isolation or after 7 days of homestay, one should contact NHS 111 online at 111.nhs.uk, call NHS 111 or dial 999 for a medical emergency. NHS 111 number also works in Scotland, Wales and Northern Ireland. In Scotland, you can also call your GP surgery.
So far, there are no vaccines or antiviral drugs that may prevent or treat human coronavirus infections. Therefore, the efforts of global health authorities have focused on fast diagnosis, isolation of patients and the development of therapies that may alleviate the severe effects of the virus. Earlier scientists discovered Chloroquine or hydroxychloroquine could act against SARS-CoV-1 and assumed that it might cause the same effect against SARS-CoV-2. Since then, they’ve started to research its properties and potential effects.
What is Chloroquine?
Chloroquine is an oral medication discovered in 1934 by Hans Andersag and commonly used for the prevention and treatment of malaria. Sometimes it is used for amebiasis, rheumatoid arthritis, and lupus erythematosus. Chloroquine is available as a generic medication and indicated on the World Health Organization’s List of Essential Medicines.
It absorbs rapidly and almost completely into the body tissues and is excreted in the form of urea more than 50% as an unchanged drug.
How can Chloroquine act against Covid-19?
According to research by the US Centers for Disease Control and Prevention (CDC), Chloroquine can cause potent antiviral effects on SARS coronavirus in both ways — as a preventative measure and for the therapy. Moreover, it has potential for the novel coronavirus as SARS and COVID-19 are similar. The US CDC research was accomplished in primate cells with the use of Chloroquine, known for its ability to elevate endosomal pH. The study has shown that Chloroquine may be useful in preventing SARS-CoV in cells if the drug is added to the cells 24 hours before infection or 3–5 hours after infection, which indicates its antiviral effect after the formation of infection.
COVID-19 is a single-stranded, positive strain RNA virus that has a protein shell and membrane. Its genome is similar to mRNA whose primary function is to be an intermediary between the genetic information in DNA and the amino acid sequence of proteins. While going through its lifecycle, COVID-19 genome becomes double-stranded RNA with the new strand for the new mRNA.
Coronaviruses may act in multiple ways:
- Both COVID-19 and SARS viruses can regulate replication and production of their proteins and depend on the breakdown of these proteins. In short, viruses turn over the body proteins to create their proteins called nucleic acids. Hydrolysis causes low PH and break down.
- Coronaviruses have non-structural proteins that are not included in their capsid — protein shell. Non-structural proteins can control body cells and suppress the immune system just as the human immunodeficiency viruses (HIV).
- Coronavirus can encourage growth factors such as cytokines to make the growth environment in the cell more favourable.
Chloroquine has shown to inhibit the replication of the coronavirus. Due to its nitrogen structure, Chloroquine can enter cells and endosomal membranes involved in transport within the cell. Nitrogens in Chloroquine can absorb hydrogens, which prevents acidification and helps to maintain a higher pH. As a result, coronavirus can’t replicate due to high pH and disabled hydrolysis. This process constipates all events within the cells, including viral replication.
An interesting analogy is that the virus acts as a garbage facility that needs to break down and burn up the garbage. If it is not able to do that, the garbage builds up and paralyses the whole city. Any virus and cancer cells act the same way and depend on turning over the worn-out or inaccurately synthesised proteins.
If Chloroquine is taken after infection, it may cause the rapid increase of pH level and disrupt the fusion between virus and endosomes, which inhibits the infection and replication, assembly and release of the virus.
Can Chloroquine intake cause mutations?
Indeed, RNA viruses can mutate as RNA based genomes are not able to copy themselves correctly. The accumulation of mutations may result in failure of the virus or lead to a more potent mutation, such as transferring from animal to human. If the replication of coronavirus is suppressed, it may cause the virus to self-destruct. However, the risk of aggressive mutation remains.
Using Chloroquine for COVID-19 treatment, as in South Korea and China, may lead to either beneficial or harmful mutations. However, it may provide more time for global health systems to increase capacity and equipment and create a vaccine. Therefore, precautionary measures must be considered to prevent COVID-19 from becoming stronger.
Is Chloroquine safe?
Chloroquine is a prescription drug; it can cause side effects and has contraindications. Chloroquine may cause side effects, including muscle problems, appetite loss, diarrhoea, and rash. Serious side effects are vision issues, muscle damage, seizures, and low level of blood cells. The most reported side effect is chloroquine retinopathy, which can lead to permanent vision loss after intake of high doses of Chloroquine. On the other hand, retinal damage is quite rare in patients with a total dosage lower than 400g, which is reached after several years of treatment).
Chloroquine seems to be safe for use during pregnancy. It has not shown to cause any harmful effects on the fetus when used for the prevention of malaria. Small amounts of Chloroquine may be excreted in the breast milk of lactating women.
Medical professionals must be consulted before the use of Chloroquine.
Are tablets or intravenous administration more efficient?
In most cases, Chloroquine is administered in tablet form as chloroquine phosphate. When the tablet is ingested, it goes through the stomach and gets absorbed in the small intestine, before it enters the blood and the respiratory system. However, the metabolism leads to time loss and reduced chloroquine delivery to the respiratory system where it is needed.
In the case of malaria, Chloroquine is used intravenously as chloroquine hydrochloride. It enters the bloodstream directly and quickly distributes within the body. This method is thought to be more efficient as it helps to act against the virus faster and at a higher concentration in the respiratory system. However, intravenous administration for the virus needs further research.
The UK stance on Chloroquine
Chloroquine phosphate is marketed in the UK as a generic antimalarial drug by Alinter Ltd in Essex, Crescent Pharma Ltd in Hampshire and The Boots Company in Nottingham and by other companies in multiple different regions. Following the Covid-19 pandemic and the ongoing clinical trials in China, the UK government has banned the parallel export and “hoarding” of:
- AbbVie’s Kaletra / Aluvia, combination lopinavir and ritonavir, used for human immunodeficiency virus (HIV);
- Chloroquine phosphate, a generic antimalarial drug made of quinolone;
- Hydroxychloroquine, an aminoquinoline derivative with anti-infective and antirheumatic properties.
These medications are restricted to meet the needs of UK patients only.
Parallel exports happen when wholesalers buy medications placed on the market in the UK and sell them in another country within the European Economic Area (EEA). Parallel exporting and hoarding may lead to medicine shortages.
UK wholesalers and other drug companies would be allowed to export the medicines restricted for parallel export if they were explicitly manufactured for the shipping to foreign markets.
Moreover, wholesalers can continue to stockpile medications if these are part of previous arrangements with marketing authorisation holders. This includes companies creating Brexit stockpiles at the request of the UK Department of Health and Social Care.
In case wholesalers break the restrictions, they may be subjected to regulatory action by the Medicines and Healthcare products Regulatory Authority. Wholesalers’ licences may be suspended and if continued, prosecuted as a criminal offence.
Are there any other drugs that may be helpful for Covid-19?
Global pharmaceutical companies and research institutions keep searching for effective treatments for coronavirus. As clinical trials and approvals for the new medicines can take up to a year, companies are exploring the potential antiviral properties of drugs already available on the market.
Drugs for rheumatoid arthritis
Medical specialists from China have already used Actemra, an anti-inflammation drug to deter the coronavirus effects on critical patients. Tocilizumab, sold as Actemra is produced by Roche, a Swiss multinational healthcare company, operating all over the world under two divisions: Pharmaceuticals and Diagnostics. Actemra is a prescription immunosuppressive medicine used mostly for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis, a type of arthritis that causes joint inflammation and stiffness for more in kids and teens.
Chinese specialists have used Tocilizumab in 20 severe COVID-19 patients to prevent an overreaction of the immune system that may cause organ failures and death. According to China’s National Health Commission, an initial clinical trial resulted in 19 patients discharged from the hospital within two weeks and one that felt better. Actemra has been approved for use in China, but not in the US. The producer of the drug was given an emergency approval to commercialise the new and faster SARS-CoV-2 test to detect the virus that has caused the global COVID-19.
Drugmakers Regeneron Pharmaceuticals Inc. and Sanofi SA have also claimed to launch clinical trials and explore if their arthritis drug Kevzara could alleviate the symptoms of COVID-19.
HIV drugs
Experts from the University of Queensland, Australia, have claimed that HIV medication may be a potentially effective treatment for coronavirus. Lopinavir/ritonavir (LPV/r), sold under the brand name Kaletra was given to coronavirus patients in Australia which would lead to no viable coronavirus in their system after therapy.
Regular use of Kaletra can help to stop HIV progressing to AIDS and reduce the risk of infection transmission. This drug can prevent viruses from using an enzyme called protease, which allows the virus to spread. With no protease, viruses can’t produce clones needed to infect other healthy cells. The ability to stop a virus reproduction and infection spread makes Kaletra a potential coronavirus treatment. However, it is considered not that effective in more severe cases when the virus has multiplied.
However, there hasn’t been any controlled tests required to approve a new drug. Australian researchers plan to conduct extensive clinical trials across Australia.
AbbVie, the US creator of HIV drugs Kaletra/Aluvia, keeps cooperating with FDA, CDC, and European agencies to prove the effectiveness of its HIV drugs for COVID-19 and launch clinical trials of the drug. So far, AbbVie has no clinical information that the medication has been successful in the treatment of infected patients and has submitted in Chinese medical researchers to start a clinical trial of the drug.
Ebola drug
Remdesivir has been recently recognised as a potential antiviral drug that may act against RNA viruses, including SARS/MERS-CoV infection in cells, mice and nonhuman primate models. Remdesivir is a broad-spectrum antiviral medication developed by California-based Gilead as a treatment for Ebola. It has effectively treated monkeys infected with Ebola, Nipah viruses, and MERs, a different type of coronavirus. Remdesivir can incorporate into emerging viral RNA chains and cause premature termination. It can also block a protein that helps coronaviruses to produce their copies and infect patients. It is now being tested as a potential COVID-19 treatment. So far, at least two trials of the drug are underway for SARS-CoV-2 in China. In March 2020, scientists from China earlier submitted a patent for remdesivir, hoping that it will help treat coronavirus.
Remdesivir has already helped the first American coronavirus patient to relieve coronavirus symptoms. Just a day after the drug intake, there was no need in supplemental oxygen, and four days later, his fever went down.
Influenza drug
Medical authorities in China have claimed that favipiravir, also known as Avigan, a drug used in Japan to treat new strains of influenza, might be useful in fighting with coronavirus. Zhang Xinmin, an official at China’s science and technology ministry, confirmed that the drug, made by Fujifilm Toyama Chemical, had shown hopeful results in clinical trials with 340 patients in Wuhan and Shenzhen. Patients who were given favipiravir became negative for the virus after several days. Moreover, X-rays confirmed improvements in lung condition in up to 91% of the patients who were treated with the drug in comparison to 62% of those who didn’t take the medication.
Fujifilm Toyama Chemical has declined to make any comments on the drug’s efficacy. Japanese health ministry suggested the drug may not be effective in more severe cases and doesn’t work effectively if the virus has multiplied.
Verified by a Healthcare Professional
Anastasiia Myronenko
Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.
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