Updated on 24 October 2020

The novel coronavirus infection COVID-19 is rapidly spreading across the world—as of 20 August 2020, it has infected nearly 22.5 million people and killed over 788,500 people globally.

Scientists and doctors are working day and night to find a vaccine or cure for this infectious disease.

Several vaccine candidates are in the final stage of human trials. Researchers are also working on monoclonal antibodies and therapies like convalescent plasma therapy to deactivate the virus in patients. Meanwhile, scientists are also looking at pre-existing medications to prevent (prophylaxis) and/or treat COVID-19 infection.

Indeed, there has been a lot of interest in medicines like hydroxychloroquine, remdesivir, favipiravir, dexamethasone and ivermectin for COVID-19 treatment. While some of these drugs have proved to be ineffectual, others (like dexamethasone) are being used for the treatment of COVID-19 patients currently. Additionally, more existing drugs like ebselen, fenofibrate and anakinra are being tested for COVID-19.

This article is about all such drugs that scientists are trying (or have tried) to repurpose in the hope of finding a treatment for COVID-19 infection.

  1. Remdesivir for COVID-19 infection
  2. Rheumatoid arthritis drug Baricitinib for COVID-19 infection
  3. Anti-parasitic drug Ivermectin for COVID-19 infection
  4. Japanese flu drug Favipiravir for COVID-19 infection
  5. Malaria drug Hydroxychloroquine for COVID-19 infection
  6. Tissue plasminogen activator for COVID-19 infection
  7. Antiviral drugs for COVID-19 infection
  8. Antidepressant fluoxetine for COVID-19 treatment
  9. Steroid dexamethasone for COVID-19 treatment
  10. Famotidine for COVID-19 infection
  11. Aspirin for COVID-19 infection
  12. Acalabrutinib for COVID-19 infection
  13. Disulfiram for COVID-19 infection
  14. Metformin for COVID-19 infection
Doctors for COVID-19 treatment: Scientists are trying out these pre-existing drugs to find a cure

Remdesivir for COVID-19 is made in India by Hetero and Cipla - in June 2020, the pharmaceutical companies launched the antiviral medicine as Covifor and Cipremi, respectively. Cipla’s Cipremi, however, has been launched with a caveat that it must only be given to patients who are on oxygen support. Two other pharma companies - Jubilant and Mylan - are also working on the production of remdesivir in the country.

Remdesivir was developed by the Gilead Sciences during the 2013-16 outbreak of Ebola but it failed to work on the Ebola virus. In 2017, Gilead scientists tested the same drug against coronavirus infections (there are at least seven that affect humans).

The research was done in laboratories (test tubes) and on rhesus macaque monkeys who were given the MERS-CoV infection (since an outbreak in 2012, Middle Eastern Respiratory Syndrome has make 2,494 people sick and killed 858 people across 27 countries according to the WHO).

The research showed that Remdesivir shut down viral replication in MERS by hindering the enzyme RNA polymerase - the enzyme is necessary for the virus to multiply and grow in the host's body.

Scientists later said that Remdesivir could inhibit the Severe Acute Respiratory Syndrome (SARS) and MERS viruses.

COVID-19 is caused by SARS-CoV-2, from the same coronaviridae family of single-stranded RNA viruses that cause SARS and MERS. Studies show that Remdesivir can reduce the typical duration of hospital stay by about four days in patients with severe COVID-19. (Human trials for this had begun as early as April 2020.)

Read more: Ebola drug Remdesivir reaches the human trial phase for COVID-19 treatment

There are many drugs which have been used for the treatment of rheumatoid arthritis such as baricitinib, fedratinib, ruxolitinib and tocilizumab. According to a recent study published in The Lancet, scientists have found that the combination of baricitinib with antivirals such as lopinavir, ritonavir or remdesivir can potentially kill the COVID-19 virus. This has not been used on patients yet but is in the clinical testing phase.

Another anti-inflammatory drug, tocilizumab, is also being used by scientists to treat the symptoms of COVID-19. According to a Chinese case study, after the administration of tocilizumab in 21 Chinese patients suffering from severe COVID-19 pneumonia, their biomarkers improved. 

Tocilizumab is a humanized IgG1 monoclonal antibody which mimics the antibodies that are produced by the immune system of the body to fight against the bad cells that enter the body. Tocilizumab binds to the IL-6 receptor, which causes inflammation in the body, and deactivates it. Tocilizumab injections are in clinical trials, known as TOCIVID-19, to test the efficacy and safety for the treatment of COVID-19 linked pneumonia. The trial started on 19 March 2020 is expected to be completed by 19 December 2022.

In recent research done by the Monash Biomedicine Discovery Institute (BDI) and the Peter Doherty Institute of Infection and Immunity (Doherty Institute), it was concluded that there is a potent anti-parasitic drug, Ivermectin, which has the ability to kill the COVID-19 virus within 48 hours. Ivermectin is an anti-parasitic drug which is used for the treatment of head lice and intestinal worms.

This joint venture of the University of Melbourne and Royal Melbourne Hospital found that when the drug, Ivermectin, was tested in labs, it arrested the growth of SARS-CoV-2 virus present in a cell within 48 hours.

The head of the study, Dr Kylie Wagstaff, stated that the drug destroyed all the RNA of the virus within 48 hours.

Ivermectin has previously been shown to be effective in labs against the viruses that cause dengue, influenza, Zika and even HIV. Ivermectin is yet to be tried on humans and is in the pre-clinical phase for use in COVID-19 treatment as of 14 April 2020.

Favipiravir was developed by a Japanese pharma company, Fujifilm Toyama Chemical, to treat influenza and got approval as an experimental treatment for COVID-19 infections in February.

China's science and technology ministry on 17 March 2020 said that the drug has been effective in treating at least mild to moderate cases of COVID-19 infection: the drug had been used on almost 340 infected people. As per the doctors, the drug prevented the replication of the virus and also improved the condition of the lungs that was confirmed by X-rays.

A randomised control clinical trial that started on 5th March 2020 to test the effect of Favipiravir along with chloroquine on 150 people with COVID-19 infection, is expected to be complete by 25th June 2020. Another clinical study was started 25th March 2020 to test the safety and efficiency of Favipiravir alone on COVID-19 patients. The study included 100 patients and is estimated to be complete by July 2020.

Infectious disease experts have pointed out that when a new pathogen wreaks havoc, doctors sometimes use drugs for off-label purposes: meaning, they use drugs for something other than the treatment for which these medicines have been approved. It is up to scientists to then take the doctors' findings and do control clinical trials to determine the efficacy and safety of the drug.

India's Glenmark Pharmaceuticals launched FabiFlu, based on the active salt used to make Favipiravir, in the country to treat COVID-19 patients who were displaying mild to moderate symptoms of the infection.

To find an effective drug against the COVID-19 virus, scientists examined the malaria drug, hydroxychloroquine, in labs and in-vivo studies. Pre-clinical data showed that hydroxychloroquine is effective in preventing COVID-19 infection. 

Hydroxychloroquine is the first-line drug used for the treatment of malaria. It also acts as a disease-modifying anti-rheumatic drug (DMARD). It is also used frequently to reduce the swelling and pain of arthritis. It has immunosuppressant properties and is used for some autoimmune diseases like lupus and rheumatoid arthritis.

The Ministry of Health and Family Welfare of India has allowed doctors to prescribe hydroxychloroquine as a prophylactic drug. However, it should only be given to those who are in direct contact with a COVID-19 positive person and to people who are at high risk of developing the disease such as healthcare workers.

Read more: Hydroxychloroquine for COVID-19: WHO resumes trial after Lancet study draws flak

Many patients with severe symptoms of COVID-19 in China and Italy died because of the clotting of blood in their lungs - which, in turn, caused a pulmonary embolism. A blood clot is one of the major reasons for respiratory failure in people as it restricts oxygen supply to the blood.

Scientists are thinking of using tissue plasminogen activator (tPA) for resolving this clot. tPA is a protein which helps in breaking down blood clots. It is widely used in the treatment of people suffering from a heart attack or a stroke as it resolves the blood clot present in their heart and brain, respectively.

The US Food and Drug Administration has granted scientists permission to directly start an experimental clinical trial to test the effectiveness of tPA for COVID-19 patients.

Read more: Causes of death in COVID-19

So far no antiviral drugs have proved to be effective in controlling the COVID-19 infection in people. Interferons are a type of signalling proteins that are produced by the body’s cells as a defensive response to the viruses. They act as a medium of contact between cells.

Scientists have been using an antiviral drug, ritonavir, in combination with the immunomodulatory agent interferon beta-1 (IFNβ-1). IFNβ-1 has been used for more than 20 years for the treatment of patients with multiple sclerosis. The combination of ritonavir and IFNβ-1 has proved to be a safe and easy course of treatment against COVID-19 in the early stages of infection. The combination drug has only been tested in labs and is yet to go under human trials.

Fluoxetine or Prozac is a well-known antidepressant that is prescribed in conditions like anxiety, depression and obsessive-compulsive disorder.

Scientists became interested in fluoxetine for COVID-19 treatment for a different reason, though: previous studies in animal models and cell cultures (human cells in a lab) had already shown that fluoxetine can a block interleukin-6 (IL-6), a pro-inflammatory cytokine.

Cytokine storm—an exaggerated immune response in which the body produces an overabundance of cytokines to fight the SARS-CoV-2 coronavirus—has been linked to severe illness and even death in COVID-19. 

Now, trials are on to check the effectiveness of fluoxetine to prevent a cytokine storm: researchers at the University of Toledo Health Science Campus are running a clinical trial on this from 1 May 2020 till about 20 April 2021, while Washington University School of Medicine researchers expect to complete their double-blind, placebo-controlled trial by 1 August 2020.

In June 2020, scientists at the Institute of Virology and Immunobiology in Germany also said that they had found that 0.8 µg/mL of fluoxetine could prevent a cytokine storm in COVID-19 patients (their findings are yet to be reviewed by peers).

In the past, fluoxetine has also been effective against viruses like enterovirus, coxsackievirus and dengue virus.

Also known as decadron, dexamethasone is a corticosteroid that may help to reduce inflammation in COVID-19 patients with acute respiratory distress syndrome.

In March 2020, the UK's RECOVERY trial started looking into the efficacy of a low dosage of dexamethasone to prevent death in severely ill COVID-19 patients. The randomised control trial, which included more than 11,500 patients, found that a dosage of 6mg of dexamethasone per day for 10 days could reduce mortality in people who were on ventilator support. The drug, however, did not have a significant effect on those patients who did not need supplemental oxygen. The findings were yet to be peer-reviewed as of 19 June 2020.

Attention: dexamethasone should never be taken without a doctor's recommendation, as corticosteroids suppress the immune function and may make the infection worse in some cases.

Famotidine is an over-the-counter available drug for heartburn which blocks the H2 receptor antagonists, which produce acid in the stomach. In a research conducted by the scientists from China, it was found that patients in Wuhan who happened to be taking this low-cost heartburn medication seemed less likely to die from or to be intubated during severe COVID-19.  

Though the mode of action for famotidine is not clear, it is believed that it possibly binds to the papain-like enzyme, which is essential for the entry of SARS-CoV-2 into the human cells. This drug has low toxicity and bioavailability and is being tested for its efficacy against COVID-19.

According to recent research, aspirin, an inexpensive, easily accessible medication can help in preventing severe complications and in-hospital mortality due to COVID-19 infection. The research found that the anti-inflammatory properties of aspirin may have protective effects on the lungs.

It was found that aspirin can help in reducing the production of immune cells such as interleukin-6 (IL-6), C-reactive protein (CRP), and macrophages in patients with pre-existing cardiovascular disease. Aspirin was found to reduce the incidence of a cytokine storm, which is one of the major reasons for severe symptoms and even death in a COVID-19 patient. 

A recent study published in the journal Immunology on 5th June 2020 showed that the new cancer drug, acalabrutinib, can help in relieving the symptoms of respiratory distress in patients with severe COVID-19. The study showed that acalabrutinib helped in reducing the levels of interleukin-6 (IL-6) in the blood which is otherwise responsible for producing inflammation in COVID-19 patients. 

On providing the cancer drug to the patients, their oxygen levels improved and their inflammation reduced. It was also found that after receiving the drug, the lymphocyte (a type of white blood cell which fights infection) count also improved significantly. 

In a study conducted by a team of chemists from Zelinsky Institute of Organic Chemistry and HSE University in Russia, it was found that disulfiram, a drug used to treat alcoholism can help in fighting COVID-19 infection. On examining the effect of the drugs, it was found that disulfiram is a sulfur-containing drug, which can effectively bind to the active site of Mpro. Mpro is an enzyme that is required by the SARS-CoV-2 virus to multiply inside the human cells. 

The scientists found that disulfiram acts as inhibits the Mpro enzyme by binding to the target site and prevents it from functioning properly. Disulfiram also helps in preventing the reduction of glutathione (an antioxidant) in COVID-19 patients, which is otherwise required for the management of coronavirus disease.

Metformin is an anti-hyperglycemic drug which is used by diabetics to reduce their postprandial glucose levels (after meal) and to maintain their basal blood glucose levels. However, not many people know that metformin was initially formed to deal with influenza in people but ended up reducing the blood glucose levels. 

In recent research, scientists found that metformin reduces the levels of TNF-alpha (an inflammatory mediator), thus reduces inflammation and cytokine storm in the body. However, consumption of metformin is linked with the risk of developing a serious condition called lactic acidosis.

Dr. Arun R

Dr. Arun R

Infectious Disease
5 Years of Experience

Dr. Neha Gupta

Dr. Neha Gupta

Infectious Disease
16 Years of Experience

Dr. Lalit Shishara

Dr. Lalit Shishara

Infectious Disease
8 Years of Experience

Dr. Alok Mishra

Dr. Alok Mishra

Infectious Disease
5 Years of Experience


Medicines / Products that contain COVID-19 treatment: Scientists are trying out these pre-existing drugs to find a cure

References

  1. Cascella M, Rajnik M, Cuomo A, et al. Features, Evaluation and Treatment Coronavirus (COVID-19) [Updated 2020 Mar 20]. In: StatPearls [Internet].
  2. The Ministry of Health and Family Welfare. Govt. of India. Advisory on the use of hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection. [Internet]
  3. The Ministry of Health and Family Welfare. Govt. of India. MINISTRY OF HEALTH AND FAMILY WELFARE (Department of Health and Family Welfare) NOTIFICATION. [Internet]
  4. Science Direct (Elsevier) [Internet]; COVID-19: combining antiviral and anti-inflammatory treatments
  5. Sallard, Erwan et al. Type 1 interferons as a potential treatment against COVID-19. Antiviral research, vol. 178 104791. 7 Apr. 2020.