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There are reasons to be optimistic about the therapies being tested

My article for The Spectator:

A striking feature of Covid-19 is how medieval our response has had to be. Quarantine was the way people fought plagues in the distant past. We know by now that it will take many months to get a vaccine, whose job is to prevent you getting the disease. But what about a cure once you have caught it: why is there no pill to take? The truth is that, advanced as medical science is, we are mostly defenceless against viruses. There is no antiviral therapy to compare with antibiotics for treating bacteria.

Arguably, virology in 2020 is where bacteriology was in the 1920s. At the time, most of the experts in that field — including Alexander Fleming and his mentor, the formidable Sir Almroth Wright (nicknamed Sir Always Wrong by his foes) — thought a chemical therapy that killed bacteria without harming the patient was a wild goose chase. Instead, they argued, theway to fight bacteria was to encourage the body’s immune system. ‘Stimulate the phagocytes!’ was the cry of Wright’s semi-fictional avatar Sir Colenso Ridgeon in George Bernard Shaw’s play The Doctor’s Dilemma (referring to white blood cells). Vaccines should be used to treat as well as prevent infections, thought Wright and Fleming. Fleming then turned this theory upside down with his discovery of penicillin in 1928.


There are two reasons for this failure to have anything on the shelf that can be used to treat viruses: one biological, the other economic. The biological problem, as Amesh Adalja of Johns Hopkins University argued in a prescient call to arms just before the pandemic struck, is that viruses do not have their own biochemistry, because they borrow ours.

So unlike, say, tuberculosis, there is not much to attack. As any doctor will tell you, antibiotics are no use in fighting a virus. They interfere with machinery found only in bacteria, but there is no equivalent machinery in viruses — which are just a bunch of genes (15 of them in the case of Sars-CoV-2) that borrow our body’s machinery to replicate themselves.

The problem is that viruses differ from each other, so treatments that work for one seldom work for another. The drugs that work against HIV-1, the main cause of Aids, sometimes do not even work against HIV-2,a milder version of the virus. Those that work against herpes don’t kill the very similar cytomegalovirus. One influenza drug works only against influenza A and not B. One antiviral kills just one genotype of hepatitis C. It is no coincidence that the antiviral treatments capable of attacking more kinds of virus, such as ribavirin, are also the most toxic to the patient, because they tend to attack the machinery of the host as well.

This is where the economic argument comes in. Highly specific drugs do not repay the vast sums necessary to get them through clinical trials to prove their efficacy. Many viruses lay out patients for only a short time — perhaps a matter of days. So patients do not come back for repeat prescriptions, further denting the incentive to develop the drug. Aids and herpes are long-lasting exceptions — sexually transmitted diseases need to lie low inside your genes to give you time to move on to a new partner — which is why they have attracted attention from pharmaceutical firms. By the time some drugs were ready to be tried against ebola in the 2014-15 epidemic in West Africa, it was over.

Protease inhibitors

None the less, the battles against HIV, ebola and Sars have left us with many more candidates for curing Covid-19 than we would otherwise have. The long search for Aids cures was eventually won with the help of drugs called protease inhibitors, which work by preventing the ‘cleavage’ (precise breaking) of a protein molecule, essential to the manoeuvre by which the virus gets into a cell.

Protease inhibitors tend to be highly specific, so the HIV ones are not necessarily useful against Sars-CoV-2. A different protease inhibitor, however, called camostat mesylate, already approved for use in Japan as a treatment for pancreatitis, is showing promise. It was found in 2012 to work against Sars in the laboratory. If successful, camostat mesylate will be useless against most other viruses, making it unprofitable in normal times, but in a pandemic of this size, Japan’s Ono Pharmaceutical won’t be out of pocket.


Invented by Gilead Sciences, the California firm that developed several HIV therapies, this compound fools the cell into using a fake version of a particular molecule when copying the virus’s genes, which are made of an alternative version of DNA called RNA. In theory such a trick should work against any virus that uses RNA for its genes and should not hurt patients because their genes are made of DNA. In 2015 remdesivir worked against ebola in monkeys, but in the 2018 epidemic in Congo it failed to make sufficient difference to ebola patients compared with other treatments.

In the lab, remdesivir kills a variety of coronaviruses and a recent report found that it cured cats of a coronavirus infection. During the current epidemic, it has been rushed into treatment on a compassionate-use basis in America for people who are dying. Preliminary results are promising and have caused a flurry of recent optimism, and the results of larger, controlled trials are eagerly awaited. However, remdesivir is unlikely to be the silver bullet because it is probably best if taken early in the infection, but you would not want to take it if you had a mild bout. It’s administered intravenously and has some nasty side effects.


There is more hope for favipiravir, sold as Avigan, one of the few antiviral treatments showing promise against more than one kind of virus. Bizarrely, it’s made by a subsidiary of Fujifilm, which diversified into chemicals and pharmaceuticals to avoid the fate of Kodak. Invented during the search for a herpes cure, it has since shown promise against influenza. Though good in the laboratory, it was only partially effective against ebola in Guinea in 2014, but initial trials on 80 coronavirus patients in China this year have suggested that it can speed up the recovery time for Covid patients, perhaps cutting it in half. So Fujifilm is now rushing to increase production and the drug has been cleared for use against coronavirus in Japan. The good news is it’s a pill, not an injection, and has few side effects except in pregnant women, where it is not safe.

The urgency surrounding a viral pandemic is fertile soil for exaggeration. Tamiflu, for influenza, is one of the world’s best-selling drugs, and governments spent billions acquiring stockpiles of it during the 2009 swine flu panic, to the benefit of Roche in particular. A lengthy campaign by the British Medical Journal has challenged the effectiveness of Tamiflu, pointing out that it has not been shown to work in randomised controlled trials. The drug’s defenders say this is unfair, as the medication’s partial effectiveness is so well established that it is now unethical deliberately to give half the patients in the trial no drug. In any case Tamiflu will not work against coronavirus: it targets an enzyme only used by influenza.

Monoclonal antibodies

If chemical treatments do not work, so-called monoclonal antibodies might. If someone recovers, their own body produces antibodies that smother the virus. These days it’s possible to mass-produce exact copies of the antibodies that work, using genetic engineering. Known as monoclonal antibodies, they proved to be the best way to treat ebola patients in Congo in 2018, when the US biotech firm Regeneron came up with a cocktail of human antibodies using genetically engineered mice. Regeneron has rushed a new cocktail of Covid-19 antibodies through the same procedure and hopes to have it ready to test in early summer. Scaling it up for mass production will not, however, be as easy as it would for a chemical pill.


French studies suggest that hydroxychloroquine, the malaria medication championed by Donald Trump, may well be at least a partial cure, especially if used in conjunction with the antibiotic azithromycin. But clinical trials are still awaited. It is not yet clear how it works: after all, malaria is neither a virus nor a bacterium, but a parasite. But hydroxychloroquine is used against rheumatoid arthritis and the autoimmune disease lupus. In the laboratory, it does seem to slow and inhibit the infection of cells by this coronavirus.

Hydroxychloroquine also tends to team up with the metal zinc and there are persistent and reliable reports that zinc either stops viruses replicating or helps the immune response to them. A gold-standard review of clinical trials found that zinc lozenges do shorten the duration of a cold by somehow interfering with virus replication. This does not just seem to be a diminishing-returns effect whereby having too little zinc, like having too little vitamin D, is bad, but once you have enough, having even more is no better. But if it is, up to a quarter of people in developing countries are deficient in zinc, and zinc deficiency is not uncommon among the elderly in western countries, so this may be part of the explanation why some elderly people are more seriously affected. In short, zinc supplements as a cheap medication, unrewarding to big pharma and therefore neglected, cannot be ruled out as a useful thing to try. Intriguingly, too much zinc kills your sense of taste, as does Covid-19 in many cases.

Altogether, I am now optimistic that within a month or two, one of the 30 or more therapies currently being tested is likely to prove effective and safe. Primed by Aids and ebola, we know where to look for chemicals that inhibit viruses, or prevent viruses replicating, in a way that we did not 20 years ago. If people can take a pill that drastically reduces their chances of dying, and clears up their symptoms before they need to be admitted to hospital, then we may not have to wait for a vaccine to end the lockdown and achieve herd immunity.

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By Matt Ridley | Tagged:  coronavirus  the spectator