The great hope of drug treatments for COVID-19, monoclonal antibodies, are failing against variants of the virus such as those identified in South Africa and Brazil, scientists and has exclusively revealed The Guardian.
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These drugs, based on synthetic clones of natural neutralizing antibodies against the coronavirus, had generated great expectations. One of them, manufactured by the biotechnology company Regeneron in the United States, was administered to Donald Trump when he tested positive for COVID-19 and may have contributed to his recovery. It is being tested in hospitalized patients in the UK.
But, to the disappointment of those working on treatments for the disease, the top three candidates – Regeneron’s and the drugs from the companies Eli Lilly and GlaxoSmithKline – fail against one or more than one of the variants.
Antibodies have huge advantages as treatments, says Nick Cammack, who heads the COVID-19 Therapeutic Accelerator (CTA) at the British Wellcome scientific foundation. They are obtained from the cloning of a human white blood cell and mimic the effects of the immune system. They are very safe, they are specifically designed to attack the virus and their use seemed very promising in the initial phase of the disease to stop its progression.
“The problem came at Christmas, when these new variants appeared, especially those from South Africa and Brazil. The changes that the virus undergoes in its S proteins discard these antibodies. So I would say that, basically, we have lost most of the antibody treatments against COVID-19 – which are the cutting-edge treatments against COVID-19 – the great hope, for the South African and Brazilian variants, “he says.
GlaxoSmithKline’s treatment continues to work against these variants, but not against the one found in Kent, UK. But with the coronavirus mutating as much as it has already, Cammack doesn’t expect current drugs to be effective for long.
They continue to work against the original virus
Researchers now have to find “conserved” regions of the virus that do not mutate in order to attack them with antibodies. “I think it’s pretty clear that while we see variants in South Africa, the UK and Brazil, there will be others. And we need massive sequencing, genetic sequencing of the virus around the world, which will reveal where the changes are occurring and also where the regions are. preserved, “says Cammack.
The drugs continue to work against the parent virus and are being used in Europe and the United States.
Monoclonal antibodies are used to attack the protein S (Spike) of the virus that attaches itself to cells in the human body. In general, the expert explains, that region of the virus does not change much, because if it does, it does not adhere as well to cells.
“Well, here we find a virus that undergoes a change that actually helps it adhere even better to the cell even better. So these monoclonals are lost,” says Cammack. “So, in a way, we go back to the starting box, honestly.”
The published scientific data on variants and monoclonal antibodies is limited: there is a pre-publication from South Africa and another from China. More articles are expected in the coming weeks.
Expensive and difficult to produce
Monoclonal antibodies “are one of the most powerful tools in modern medicine”, according to a recent Wellcome report on expanding access to the population of low- and middle-income countries. They are used in cancers and autoimmune diseases, such as rheumatoid arthritis, and are being tested against HIV.
But they are expensive and relatively difficult to produce, so only rich countries have really benefited from them so far.
The hope, according to Lindsay Keir, author of the report, is that COVID-19 could be a catalyst in getting them to the rest of the world. “COVID-19 has revealed the potential for them to be used for other diseases as well, such as infectious ones. But we have not yet been able to offer a simple way for monoclonal antibodies to be accessible to everyone.” There are already more antibody treatments in COVID-19 trials, he says. “It’s not about starting from scratch.”
Faced with the challenge, the companies are working together, Cammack says. Combination drugs, like the one in the trial announced last week by GlaxoSmithKline and Eli Lilly, could be an important part of the answer.