Testing times: Developing medications to combat the novel coronavirus

It’s not all bad news on the novel coronavirus front, even though, according to some estimates, five per cent of all those infected will need intensive care support. If the spike in infections occurs too quickly, it could overwhelm healthcare systems. And that is why, while a vaccine is at least a year away, developing a treatment protocol, which can be a mix of medications and medical procedures, to mitigate the devastating respiratory illness remains a priority.

Drawing upon years of basic and clinical research, academic institutes and pharmaceutical companies are racing towards developing multiple strategies to combat SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which causes Covid-19. These range from diagnostics and existing and novel antivirals to vaccines. The development of new drugs is a lengthy process, which is why most of the current clinical trials have focused on re-purposing or finding new uses for existing drugs or therapeutic approaches that are known to be safe. What remains to be learnt is if these drugs are effective for the treatment of the SARS-CoV-2 infection.

The trials have drawn upon prior work on previously encountered species-hopping (zoonotic) coronaviruses, closely related to SARS-CoV-2, that have caused fatal respiratory disorders. These were SARS-CoV-1, which caused the outbreak in 2002, and the Middle eastern respiratory syndrome CoV (MERS-CoV) of 2012, jumping to humans from bats and camels, respectively, and known to infect other species such as civets. All three are RNA viruses, of a class called beta-coronaviruses.

One of the drugs in Phase III clinical trials in China, also given to a few US patients on compassionate basis, is the antiviral Remdesivir (Gilead Sciences), originally developed for treatment of Ebola. It works by blocking the RNA-dependent RNA Polymerase (RdRp) required for viral replication. Remdesivir has been shown to prevent and reduce symptoms of MERS-CoV in monkeys and SARS-CoV-1 in mice. Recent studies on human cells have also shown antiviral efficiency against SARS-CoV-2. Trials are ongoing in China, Korea and the US. The earliest results from these trials are expected in April 2020.

Surprising to researchers, HIV drugs, which inhibit the spread of the human immunodeficiency virus in a patient, have also shown some promising results in some patients. Even when the mechanism by which they work is unknown, this report has led to many of the existing HIV drugs (Lopinavir, Ritonavir) being used in different combinations with other antivirals such as flu drugs (Arbidol, Favipiravir) in clinical trials. Using combinations of drugs, or cocktails, is common practice for combating complex diseases such as AIDS.

A cheap and readily available antimalarial drug, Chloroquine, has also shown efficiency against SARS-CoV-2, and is being tested in trials. It could resolve the issues of inherent cost of production and other intellectual property issues that go hand-in-hand with using other proprietary drugs.

Another broad class of drugs is biologics, which have driven the explosive growth of the biotechnology industry in the past two decades. These are expensive to manufacture, but Indian manufacturers have caught up in this sector. Antibodies (Abs) are the weapons produced by our bodies to kill disease-causing viruses or bacteria and also to inactivate the toxins they release. These Abs constitute a large part of our “immunity”. It is possible to harvest these antibodies using genetic engineering from the blood of patients who have recovered from Covid-19, as they used their immunity and Abs to fight it off. These would be specific to SARS-CoV-2 and are already in development by an American company, Vir Biotech.

Another off-label biologic drug, Actemra (Roche), has been approved by the Chinese government to combat the severity of lung injury which is caused by the body’s own immune system attacking the lungs, in patients with SARS-CoV-2 pneumonia. Actemra is USFDA-approved for the treatment of rheumatoid arthritis, which is also a condition where the body causes self-harm. US clinical trials will start soon.

A vaccine (mRNA-1273) developed by Moderna, a Massachusetts-based biotechnology company, was the first to enter a clinical trial in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) in the US. But testing and scale-up in production could take well over a year.

“Antiviral drugs like Remdesivir have the best potential for being immediately useful, as scaling up their production is the easiest,” says Vinay S Mahajan, an immunologist and pathologist at Harvard’s Brigham and Women’s Hospital. “At times like this, securing access to these drugs should be the main focus of governments and biotech or pharmaceutical companies alike.”

He points out that the Serum Institute of India, one of the leading manufacturers of vaccines in the world, is in the race, seeking to make a vaccine whose production can be scaled up for an entire population. “But it will take time. Firm determination and a coordinated response by the pharmaceutical industry, the government, and the cooperation of the people are needed to bring this epidemic under control, or at least delay it until solutions are developed across the globe,” he says.

Hospitals, he adds, are beginning to cancel all elective surgeries (procedures that do not involve a medical emergency) and plans are in place to convert operating rooms into ICUs, if the need arises.

“Time is of the essence,” Dr Mahajan says. “Hospitals in India need to make plans to build the capacity and plan for the possibility of a sudden increase in the number of patients who need ventilators. The red tape will need to go down. Hospital laboratories should be allowed to run their own tests. The developers of tests, antivirals and vaccines need to be given a free hand. They need to be offered full support and greater incentives to accelerate their programme. In the US, regulatory delays created significant hurdles in responding to the epidemic. India cannot afford to repeat the same mistake.”

While social distancing is not a practical option for large parts of the Indian working class earning daily wages, there has never been a better time for sharing streaming services accounts with retired parents, grandparents and neighbours.

Ishita Das is a US-based neuroscientist and writer