The great hope for drug treatments against Covid-19, monoclonal antibodies, is failing against variants of the virus, such as those that have emerged in South Africa and Brazil, scientists have discovered.
There have been high expectations of drugs. One, made by Regeneron in the United States, was given to Donald Trump and may have played a role in his recovery. It is being tested in hospital patients in the UK.
But to the dismay of those working on therapeutics against the disease, the top three contenders – Regeneron and the drugs from Eli Lilly and GlaxoSmithKline – fail against one or more of the variants.
Antibodies have huge advantages as treatments, said Nick Cammack, who leads the Covid-19 therapeutic accelerator at Wellcome. They are derived from the cloning of a human white blood cell and mimic the effects of the immune system. They are very safe, specifically designed to attack the virus, and their use seemed very promising in the early stage of the disease to stop its progression.
“The challenge came at Christmas when these new variants appeared, particularly those from South Africa and Brazil. The changes the virus makes to its spike proteins actually remove these antibodies, ”he said.
“Basically most of the cutting edge antibody therapies for Covid, which are the cutting edge therapies for Covid, I must say, so the great hope, have been lost for the South African and Brazilian variants.”
GlaxoSmithKline’s treatment still works against those variants, but not against the one that emerged in Kent in the UK. But with the coronavirus mutating as much as it already has, Cammack doesn’t expect any of the current drugs to be effective for long.
Researchers now need to find “conserved” regions of the virus that do not mutate to attack with antibodies. “I think it’s pretty clear, although we’ve seen variants from 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 made and also reveal where the conserved regions are, ”he said.
The drugs still work against the original virus and are used in Europe and the United States.
Monoclonal antibodies were chosen to target the spike protein of the virus that attaches itself to cells in the human body. In general, he said, that region of the virus doesn’t change much, because if it does, it won’t adhere as well to cells.
“Well, here we are with a virus that makes a change that actually helps it adhere even better to the cell. So these monoclonals have been lost, ”Cammack said. “So we’re back where we started a bit, honestly.”
Monoclonal antibodies “are one of the most powerful tools in modern medicine” according to a recent Wellcome report on expanding access to people in 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 manufacture, so only rich countries have really benefited from them so far. The hope, said Lindsay Keir, author of the report, is that Covid can be a catalyst to bring them to the rest of the world.
“Covid has highlighted the potential for them to be used for other diseases as well, such as infectious diseases. But we have not yet been able to show a simple way to make monoclonal antibodies accessible to everyone, “he said.
There are already more antibody treatments in the Covid trials, he said. “It’s not about starting from scratch.”
In the face of the challenge, the companies were working together, Cammack said. Combination drugs, such as the trial announced last week by GlaxoSmithKline and Eli Lilly, could be an important part of the answer.
George is Digismak’s reported cum editor with 13 years of experience in Journalism