Tag Archives: drug discovery

Small study showed colchicine improved outcomes in COVID-19 patients

A small randomized, double-blind clinical trial published in RMD Open showed colchicine to be safe and effective in treating moderate to severe COVID-19 infections in hospitalized patients. In the study, patients who took the inexpensive drug required supplemental oxygen and hospitalization for less time. This is the first randomized controlled trial (RCT) on colchicine for COVID-19.

Colchicine is most commonly used to prevent attacks of gout or pseudogout arthritis, which are types of arthritis caused by a buildup of crystals in the joints. Blood cells travel to these areas of inflammation, causing pain and swelling. Colchicine prevents white blood cells from traveling into these areas and therefore helps to reduce pain and tenderness.

Colchicine can also be used to treat acute attacks when nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen or ibuprofen cannot be used for safety reasons or have been ineffective. Colchicine is an alkaloid naturally occurring in Colchicum autumnale a plant of Liliaceae family.

Now, it has also been shown to be effective against COVID-19.

From April 11 to August 30, 2020, 72 Brazilian patients received either a placebo or 0.5 milligrams of colchicine three times a day for 5 days followed by the same dose twice a day for 5 days in addition to a standard COVID-19 treatment of azithromycin, hydroxychloroquine, heparin, and (after the RECOVERY Collaborative Group results were announced) glucocorticoid. Methylprednisolone was given if supplemental oxygen was 6 liters per minute or higher.

The most common side effect was diarrhea (16.7%), and colchicine doses were adapted if the patient weighed at least 176 pounds (80 kilograms) or had chronic kidney disease. Those on colchicine needed oxygen for an average of 4 days and stayed in the hospital for an average of 7 days; whereas, the control group needed oxygen for 6.5 days and stayed 9 days. The drug’s effect on ICU admission or mortality rate was not quantified, although the researchers note that 1 patient in the colchicine group went to the ICU compared with 3 in the placebo group. Two patients died in the study, both in the placebo group.

While the researchers acknowledge these results are not yet generalizable (34 of 35 patients receiving colchicine were overweight or obese), they concluded colchicine’s ability to slow systemic inflammation is promising. Systemic inflammation is the hallmark of hospitalized patients due to COVID-19. There is no specific treatment but supportive care and attempts to control the immune activation improve the clinical picture. By diminishing the activation of leucocytes, colchicine may be an intervention worthy of being tested further in more patients.

Can old drugs be used to treat COVID-19?

Finding new uses for existing drugs is a good strategy, especially in our fight against COVID-19 for which there is no treatment.

These drugs have already been produced and tested in patients for different indications, which means we can save valuable time.

Some promising treatments

By attacking different parts of the virus, antivirals can prevent a virus from entering cells or interfere with its reproduction thereby stopping the infection.

Remdesivir works by interrupting the SARS-CoV-2 virus as it copies its genetic material, which in turn stops the virus from reproducing. What’s clever about remdesivir is that it disrupts the virus but not the human cell, so it has a targeted effect. The National Institutes of Health (NIH) has started a randomized controlled trial for the treatment of COVID-19 patients with the investigational antiviral drug remdesivir. The FDA has been working with the drug manufacturer, Gilead Sciences.

Kaletra is a combination of two antiviral drugs, lopinavir and ritonavir, used to treat HIV. One of the first major studies of 200 seriously ill patients from China found no benefit with the use of Kaletra. However, it may be possible that Kaletra could work if given earlier or if given to patients who are not severely ill. The World Health Organization (WHO) has included Kaletra in a major multi-country trial launched this week.

Medical authorities in China have said a drug used in Japan to treat new strains of influenza appeared to be effective in coronavirus patients. Zhang Xinmin, an official at China’s Science and Technology Ministry, said favipiravir, developed by a subsidiary of Fujifilm, had produced encouraging outcomes in clinical trials in Wuhan and Shenzhen involving 340 patients.

Patients who were given the medicine in Shenzhen turned negative for the virus after a median of four days after becoming positive, compared with a median of 11 days for those who were not treated with the drug. Favipiravir would need government approval for use on COVID-19 patients, since it was originally intended to treat flu.

Chloroquine and hydroxychloroquine are already widely available, as they are used to treat diseases like malaria and arthritis.

Both chloroquine and hydrochloroquine have been used for many decades to treat malaria, which is caused by a parasite, unlike the coronavirus, SARS-CoV-2 causing COVID-19. Reproduction of SARS-CoV-1 (the ‘original’ SARS virus in 2002-2003) in cell culture was shown to be blocked by chloroquine in 2005, by which time there were no human infections. Recently reproduction of the newly emerged SARS-CoV-2 in cells was found to be inhibited by chloroquine.

As a consequence, a derivative of the drug, hydroxychloroquine (a less toxic derivative) has been tested in patients with COVID-19. A clinical study conducted in Marseille, France to evaluate the efficacy of hydroxychloroquine in the treatment of COVID-19 was released on 18 March 2020. Patients included in the study were all over 12 years old and had laboratory-confirmed infections with SARS-CoV-2.

The control group received the standard treatment of care (no hydroxychloroquine / HCQ). The hydroxychloroquine treatment group received oral HCQ sulfate, 200mg three times a day for 10 days. The HCQ + Azithromycin treatment group received oral HCQ sulfate, 200mg three times a day for 10 days -Oral azithromycin, 500mg on day 1, followed by 250mg daily for 4 days. Viral loads in nasopharyngeal wash were measured daily. This was a small non-randomized trial but results are promising. On Day 6, 12.5% of control patients virologically cured, 57.1% of HCQ treated patients virologically cured and 100% of HCQ + Azithromycin patients virologically cured.

The current pandemic is, no doubt, one of the most important challenges in recent times. But we are more prepared than ever to deal with it. Some of the world’s brightest minds are on it, and we are already starting to see some results.

Anti-malaria drug being tested for efficacy against COVID-19

Chinese experts, based on the result of clinical trials, have confirmed that chloroquine phosphate, an antimalarial drug, has a certain curative effect on the novel coronavirus disease (COVID-19).

The experts suggested the drug be included in the next version of the treatment guidelines and applied in wider clinical trials as soon as possible, Sun Yanrong, deputy head of the China National Center for Biotechnology Development under the Ministry of Science and Technology (MOST), said at a press conference.

Chloroquine phosphate, which has been used for more than 70 years and is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. Chloroquine was discovered in 1934 by Hans Andersag but was initially ignored for a decade because it was considered too toxic for human use. During World War II, United States government-sponsored clinical trials for antimalarial drug development showed unequivocally that chloroquine has a significant therapeutic value as an antimalarial drug.

Aside from preventing and treating malaria, chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus.

Chloroquine was selected from tens of thousands of existing drugs after multiple rounds of screening, Sun said. According to her, the drug has been under clinical trials in over 10 hospitals in Beijing, as well as in south China’s Guangdong Province and central China’s Hunan Province, and has shown fairly good efficacy.

In the trials, the groups of patients who had taken the drug have shown better indicators than their parallel groups, in abatement of fever, improvement of CT images of lungs, the percentage of patients who became negative in viral nucleic acid tests and the time they need to do so, she said.

Patients taking the drug also take a shorter time to recover, she added. Sun gave an example of a 54-year-old patient in Beijing, who was admitted to the hospital four days after showing symptoms. After taking the drug for a week, he saw all indicators improve and the nucleic acid turn negative.

Zhong Nanshan, Chinese epidemiologist and pulmonologist who discovered SARS in 2003. 

So far, no obvious serious adverse reactions related to the drug have been found among the over 100 patients enrolled in the clinical trials, she said. The expert team, led by Zhong Nanshan, a renowned respiratory specialist and an academician of the Chinese Academy of Engineering, agreed that chloroquine phosphate can be used to treat more COVID-19 patients, Sun said.

Previous in vitro experiments showed that it can block virus infections by changing the acidity and basicity value inside the cell and interfering receptors of SARS coronavirus. It also shows immune-modulating activity, which may enhance its antiviral effect in vivo and is widely distributed in the whole body, including the lungs, after oral administration.

Chloroquine is also in trials as an antiretroviral for HIV-1/AIDS and is being considered in pre-clinical models as a potential agent against chikungunya and Zika.

UPDATE: New research suggests that remdesivir — broad-spectrum antiviral agent — and chloroquine “are highly effective in the control of 2019-nCoV infection in vitro.” Scientists at the University of Queensland Centre for Clinical Research recently announced that they are close to commencing a clinical trial with chloroquine in Australia by the end of the month.

AI-designed drug will be used on humans for the first time

Credit: Pixabay.

A novel drug meant to treat obsessive-compulsive disorder (OCD) has been designed by an artificial intelligence (AI). Researchers explain that it took the AI only 12 months to find the right molecule, a process that typically takes five years for human researchers. The medicine will soon begin clinical trials, marking the first time a drug discovered by an AI will be used on humans.

The molecule, known as DSP-1181, was among billions of possible chemical combinations that the AI went through while respecting countless parameters. It’s a delicate process that typically involves a lot of trial and error, but which has been vastly accelerated by machine learning algorithms.

British startup Exscientia and Japanese pharmaceutical company Sumitomo Dainippon Pharma worked together to make this kind of AI a reality. Speaking to the BBC, Exscienta chief executive Prof Andrew Hopkins said:

“We have seen AI for diagnosing patients and for analysing patient data and scans, but this is a direct use of AI in the creation of a new medicine.”

“There are billions of decisions needed to find the right molecules and it is a huge decision to precisely engineer a drug,” said Prof Hopkins.

“But the beauty of the algorithm is that they are agnostic, so can be applied to any disease,” he added.

Researchers plan on conducting phase one trials in Japan with subsequent global tests to follow if these initial results are promising.

DSP-1181 is a long-acting serotonin 5-HT1A receptor agonist meant to treat OCD. In Japan, one million people have this condition, while the disorder is present in around 3 million people in the United States.

The British firm plans on using this AI-aided approach to discover novel treatments for other medical conditions. Researchers are currently working on drugs for cancer and cardiovascular disease.

The average cost of research and development for a new drug is $2 billion. Raising the efficiency of drug discovery is paramount in the future and, as this news story shows, AI will play a critical role.

For now, DSP-1181 is the first AI-designed drug meant to treat human diseases. However, by the end of the decade, most new drugs could be discovered by an AI, Hopkins believes.