From Malaria to HIV, scramble to find which drug works on coronavirus

Which drug can save a critical COVID-19 patient?

Researchers across the world are virtually racing against time to find an answer to this question.

Is it an anti-malaria drug first tested during World War II or a recent antiviral drug that failed in the case of Ebola outbreak or a combination drug already being used against HIV?

There is no clear answer as yet but experiments are going on at break-neck speed to find the most effective drug to save lives. The scientists are now experimenting with over 150 drugs to fight COVID-19. They include the existing FDA-approved drugs, drugs under clinical trials and preclinical compounds.

The list is long and includes some unexpected candidates such as entacapone which is used to treat Parkinson’s disease, ribavirin, an anti-viral medication which was administered to Nipah patients in Kerala during the 2018 outbreak and Hydroxychloroquine, an antimalarial drug.

The researchers are looking to repurpose drugs already approved for other diseases and known to be largely safe.

Three approaches

Broadly, three approaches are being investigated:

1) Antiviral drugs that directly affect the coronavirus’s ability to thrive inside the body.

2) Drugs that can calm the immune system – patients become seriously ill when their immune system overreacts and starts causing collateral damage to the body.

3) Antibodies, either from survivors’ blood or made in a lab, that can attack the virus.

When the virus invades the cells, it hijacks the cells’ molecular machinery to replicate itself because it cannot do this on its own. What the drugs do is to inhibit this process so that the virus can no longer use the cells for its own survival.

Scientists have suggested dozens of existing compounds for testing, but the World Health Organisation (WHO) is focusing on four most “promising” therapies: an experimental antiviral compound called remdesivir; the anti-malarial drug hydroxychloroquine; a combination of two HIV drugs, lopinavir and ritonavir; and that same combination plus interferon-beta, an immune system messenger that can help cripple viruses.

Here are the promising drugs under study:

Remdesivir: This anti-viral compound gets a second chance to prove itself. Originally developed to combat Ebola virus, it fizzled out after proving to be ineffective.

However, it has shown to work in the case of novel coronavirus. Developed by the US-based biotech company Gilead Sciences, it has already been used in some Covid-19 patients.

The latest clinical trials have been encouraging. The US National Institute of Allergy and Infectious Diseases (NIAID) found that remdesivir cut the duration of symptoms from 15 days down to 11. The trials involved 1,063 people at hospitals around the world.

Dr Anthony Fauci who runs NIAID, said that remdesivir had “a clear-cut, significant, positive effect in diminishing the time to recovery”. A WHO assessment described remdesivir as the “most promising candidate” against COVID-19.

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Remdesivir specifically targets key viral proteins involved in making new copies of the virus and prevents them from working.

However, a study, published in the Lancet Journal, said that this drug alone would not be able to treat the infection and it cannot help in reducing mortality rates. A combination of additional drugs have been used, the study recommended.

It is thought that anti-viral drugs may be more effective in the early stages, and immune drugs at a later state in the treatment of the disease.

It is one of the four drugs in the WHO-mandated “solidarity trial”.

HIV Drugs

The studies are also being carried out to see whether a pair of HIV drugs – lopinavir and ritonavir – could be effective in treating coronavirus.

There has been some evidence they can work in the laboratory, but studies in people have been disappointing.

The combination did not improve recovery, reduce deaths or lower levels of the virus in COVID-19 patients with serious symptoms.

However, as the trial was conducted with extremely sick patients, with nearly a quarter of them succumbing to the infection, it may have been too late in the infection for the drugs to work.

Anti-malarial drug

Chloroquine, and a related derivative, hydroxychloroquine, may have antiviral and immune-calming properties. The drugs have shot into limelight as potential coronavirus therapies, largely due to the unverified claims made by the United States President Trump, but the evidence about their effectiveness is very sketchy.

Laboratory tests have shown that it can inhibit the coronavirus, and there is some anecdotal evidence from doctors saying it appears to help patients.

However, the WHO says there is no definitive evidence of its effectiveness.

In fact, it might do more harm than good. The drug has a variety of side effects and can in rare cases harm the heart. In some patients, it can even block the immune response.

Studies in cell culture have suggested chloroquines have some activity against novel coronavirus but the doses needed are usually high—and could cause serious toxicities.

The US Society of Critical Care Medicine said “there is insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine in critically ill adults with COVID-19.”

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Chinese researchers, who reported treating more than 100 patients with chloroquine, said it was beneficial but the data underlying the claim have not been published. “No data has been shared regarding the chloroquine studies,” the WHO said.

Combination drugs

A combination of the three drugs—two anti-virals Ritonavir and lopinavir and interferon-beta, a molecule involved in regulating inflammation in the body, is now being tested in MERS patients in Saudi Arabia in the first randomised controlled trial.

But, the use of interferon-beta on patients with severe COVID-19 might be risky. If it is given late in the disease, it could easily lead to tissue damage instead of helping patients.

A study conducted at the Hong Kong University showed that the treatment using this combination drug involved some adverse effects including diarrhea and nausea.

In another instance, the researchers have said that camostat mesylate, a drug approved in Japan for use in pancreatic inflammation, could work to combat COVID-19, as it was found to block the entry of the virus into lung cells.

The Council of Scientific and Industrial Research (CSIR) has started a clinical trial on an anti-leprosy vaccine, Mycobacterium (Mw) , to see if it can be used for COVID-19 treatment.

Tough customers

Viruses are not as easy as bacteria to treat. That is because they are very diverse, with unique characteristics that can’t be targeted with a broad-spectrum drug like a general antibiotic.

Also, viruses hijack the human cellular machinery to create proteins that help them to replicate. So, targeting viruses while not damaging human cells can prove very challenging.

Once researchers identify the specific protein on the outside of human cells that the new coronavirus uses to gain entry, then they will be able to find small molecules that can block the binding of the virus into cells.