Abu Dhabi, UAEMonday 30 March 2020

Coronavirus and the ongoing fight against deadly disease

The WHO estimates 10 million people a year could die from antibiotic resistant infections by 2050

So small that a hundred million of them could sit on a pin-head, the Wuhan coronavirus packs a terrifying punch.

In just a matter of weeks, it has spread from a handful of patients in central China to thousands across the world – including the Emirates – and left hundreds dead.

Now the race is on to stop the virus triggering a pandemic where the death toll runs into thousands or worst. There’s no time to wait for a vaccine, which experts predict could take at least a year to develop.

Instead, scientists must focus on something far more basic. They must stop the virus spreading.

[We] need countries and the pharmaceutical industry to step up and contribute with sustainable funding and innovative new medicines.

Dr Tedros Adhanom Ghebreyesus

In truth, it makes no sense to talk of viruses dying, as they aren’t alive. They are simply strips of genetic instructions crammed into protein shells.

But unless they can break into healthy cells and hijack them to make copies of themselves, they are doomed.

The hope is that quarantining and travel bans alone will ensure 2019-nCoV - the official name of the Wuhan virus - goes the same way as the SARS coronavirus, which emerged in China in 2002.

By July 2003, more than 8,000 people had been infected, of which around one in 10 died, a far higher mortality rate than for 2019-nCoV.

Yet within a year, quarantine and travel bans had halted the spread of SARS. It’s now effectively extinct.

While this latest viral assault will most likely be repulsed, it certainly won’t be the last.

Viruses are constantly mutating, finding ways to invade human cells and making billions of copies of themselves before escaping from their hosts with deadly effect.

Yet these very traits now look set to make viruses the heroes in the war against the truly terrifying threat of antibiotic resistance.

Until the 1940s, a simple scratch could prove fatal if it became infected with bacteria. Only our disease-fighting immune system stood between us and death.

That all changed with the mass-production of antibiotics, beginning with penicillin in the run-up to D-Day in 1944.

Originally derived from mould, the compound weakens the cell walls of bacteria until they burst and die.

But barely had penicillin entered service than it started to lose its potency. Scientists found some bacteria had mutations making them less vulnerable to the antibiotic’s effects.

This allowed some bacteria to survive and pass their resistance to future generations of bacteria – which then became ever more prevalent.

The result has been the emergence of “superbugs” - life-threatening bacteria immune to all common antibiotics.

The World Health Organisation estimates that more than 700,000 people die from antibiotic resistant infections each year - around a thousand times the death-toll from SARS.

And unless more effective treatments are found, that figure is set to soar to 10 million a year by 2050.

Given the global demand, one might expect big pharmaceutical companies to be racing to find new antibiotics.

Paradoxically, the very nature of the problem is a huge deterrent. New compounds would be used only in extreme cases precisely because of the need to protect their potency.

Animals have been left behind in Wuhan, China, after owners have been quarantined due to the country's coronavirus outbreak. AFP
Animals have been left behind in Wuhan, China, after owners have been quarantined due to the country's coronavirus outbreak. AFP

Just last month, the Director-General of the WHO, Dr Tedros Adhanom Ghebreyesus, warned that far more needed to be done – and quickly.

“[We] need countries and the pharmaceutical industry to step up and contribute with sustainable funding and innovative new medicines,” he said.

Ironically, the best hope may lie not in new medicines but in a bizarre discovery made long before the first antibiotics.

In 1896, an English doctor named Ernest Hankin reported that the murky waters of the Ganges and Jumna rivers in India seemed to contain a substance that attacked the bacterium responsible for cholera.

The nature of the substance remained a mystery until 1917, when the French-Canadian microbiologist Felix d’Herelle announced the discovery of what he called bacteriophages – “bacteria-eaters”, viruses that preyed not on humans but on bacteria.

Officials in full protective gear disinfecting Indonesian students as they disembark upon the arrival at Hang Nadim international airport in Batam, following their evacuation from the Chinese city of Wuhan due to the deadly SARS-like virus. AFP
Officials in full protective gear disinfecting Indonesian students as they disembark upon the arrival at Hang Nadim international airport in Batam, following their evacuation from the Chinese city of Wuhan due to the deadly SARS-like virus. AFP

Studies suggested they were highly effective but had no side-effects. Yet doubts about their true nature and the emergence of penicillin led to “phage therapy” being largely forgotten.

It took the incredible magnification made possible by the electron microscope to reveal the true nature of phages – and another shock.

With their bulbous “head”, thin body and spindly legs, they look just like aliens from another world.

Now, after decades of neglect, phages are being seen as unlikely allies in the fight against infections from skin disease and dysentery to meningitis.

Their biggest attraction is that while bacteria can still become resistant to them, phages can also evolve, finding new ways to kill their prey.

Until now, that has required sifting through and testing huge numbers of natural phages to find those up to the job.

Passengers wear masks to prevent the outbreak of a new coronavirus in a Light Rail Transit train in Kuala Lumpur, Malaysia. Reuters
Passengers wear masks to prevent the outbreak of a new coronavirus in a Light Rail Transit train in Kuala Lumpur, Malaysia. Reuters

Now a team at the Massachusetts Institute of Technology in the United States has made a key breakthrough: a way of engineering new phages to order.

The trick lies in mass-producing phages with different types of tail fibres – the “legs” which allow them to bind to a bacterium and kill it.

In experiments recently reported in the leading journal Cell, Professor Timothy Lu and his colleagues created phages with around 10 million different types of legs and tested them against different strains of E. coli – a potentially deadly gut bacterium.

They found that the newly-engineered phages could kill even forms of E. coli with mutations that protect them against conventional phages.

Tests in mice showed that the phages not only cured infection, but also prevented the bacteria from becoming resistant.

The team is now working on creating phage “libraries” capable of tackling other bacterial diseases, and moving to human trials.

They see phages being used alongside conventional antibiotics, being called in like microscopic “special forces” to fight the toughest infections.

These bizarre-looking viruses may be a second chance for humanity to protect itself against an age-old foe. There may not be another.

Robert Matthews is Visiting Professor of Science at Aston University, Birmingham, UK

Updated: February 8, 2020 04:48 PM

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