Arsenal of drugs in works in war against virus

SCIENTISTS HAVE BEEN DEVELOPING A RANGE OF DIFFERENT TREATMENTS TO HELP SAVE LIVES

There is currently no cure for coronavirus, with the world pinning its hopes on mass vaccination to end the pandemic. Yet scientists are also racing to find treatments that could dramatically alter the course of the disease.

Already, Britain has approved dexamethasone and tocilizumab, which together can lower the risk of death in sickest patients by around 40 per cent, following U.K. trials.

So is a cure for coronavirus just around the corner? Probably not.

The problem lies in biology. Viruses are not technically alive, and use the machinery inside the cells of other organisms to reproduce. While antibiotics can kill bacteria, viruses have effectively assimilated with us, so killing them risks also harming us.

To get around the problem of not attacking the body's own cells, scientists look for proteins and enzymes that are specific to the virus. But some viruses also have an extra trick up their sleeve. They can go to sleep, hiding from the immune system until conditions are more favourable for replication in a tactic known as viral latency. In the case of HIV, it turns off the enzyme and becomes invisible. “Some viruses enter multiple human cells and just hide there,” said Dr. Julian Tang, clinical virologist at the University of Leicester.

Thankfully, many viruses such as influenza, measles, rubella and mumps are cleared away entirely, leaving some degree of immunity, and so far it seems coronavirus falls in this category. Tang said: “Most viruses are cleared by the host (patient) immune system naturally — including SARS-CoV-2.”

But immunity is often not long-lasting. The viruses also mutate, which can make vaccines redundant.

In the most severe cases, coronavirus also triggers a deadly immune storm, at which point a new kind of treatment is needed to dampen down the immune system.

So three types of drugs are being developed. One type prevents the virus from replicating, giving the immune system time to fight it off. The second boosts the immune system, while the third does the opposite, dialing down the immune system to prevent a lethal cytokine storm.

Fortunately, many viruses produce an enzyme called an RNA-dependent RNA polymerase. Nearly a decade ago, the pharmaceutical company Gilead began work on a drug called Remdesivir to target the enzyme. It was the first drug rolled out to British patients last May, and clinical trials have shown it helps patients get out of hospital four days earlier.

There is also hope that influenza antivirals such as favipiravir and molnupiravir could be repurposed in the fight against coronavirus, with small trials showing they improve lung function. Large trials are underway.

One clever antiviral treatment in the pipeline is called Recombinant ACE-2. Scientists have shown they can deploy artificial ACE-2 proteins as decoys, thereby luring the virus away from real cells. However, it has yet to be proven in animals or humans.

Drugs which boost the immune system also look promising. Scientists are testing whether the blood plasma of recovered patients could improve survival rates. Last week, a large trial by Oxford shows that blood plasma does not prevent death in seriously ill patients, but the team is waiting to see if it benefited certain subgroups.

Synthetic antibodies are also giving hope. Scientists look for people who have mounted a strong response to coronavirus then artificially replicate their immune proteins.

Eli Lilly's monoclonal antibody bamlanivimab has been shown to reduce people's risk of being hospitalized by 72 per cent and is under review by the Medicines and Healthcare Products Regulatory

Agency. Regeneron's antibody cocktail reduced trips to the hospital by 57 per cent. Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said: “They are the first antiviral drugs that demonstrably work in the first phase of the disease, just after the virus has infected someone but before it has had time to cause a lot of damage.”

Another way of boosting immunity is to give synthetic interferons, which boost the immune system while also keeping it in check. Last year, British pharma company Synairgen published results showing interferon “SNG001” lowered the risk of severe COVID-19.

For many seriously ill patients, the immune system does not need help, but requires dampening down. The steroid dexamethasone has been shown to cut deaths of severely ill patients by one third and is now given to severely ill NHS patients. This week, Oxford University produced results showing asthma drug budesonide cut the risk of requiring urgent care or hospital treatment by 90 per cent if given after the onset of symptoms.

Drugs developed for autoimmune conditions such as rheumatoid arthritis have also been found to help dampen the cytokine storm. Oxford also showed the arthritis drug tocilizumab reduces the risk of death by about 14 per cent in patients with severe COVID-19 and will be used by the NHS along with dexamethasone. It could save one in every 25 treated patients.

And another approach may be blood thinners. Observational studies suggest that people taking drugs like aspirin and warfarin do far better. LSHTM published a study showing taking blood-thinning tablets within 24 hours of hospital admission reduces the risk of death by more than a third.

So although a full cure for COVID-19 may never come, scientists are edging closer to treatments that can save lives.

NICOLAS TUCAT / AFP VIA GETTY IMAGES FILES The company ProNeem in Marseille, France, has designed an “intelligent” mask, impregnated with a virucide. There are also many approaches being developed to lessen the impact of the COVID-19 infection in the absence of a cure.