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Don't panic concerning the newest coronavirus mutations, say drug firms

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All viruses are subject to random mutations in their genetic material. Any change that offers an advantage – for example, infecting the virus with more hosts or resistance to certain drugs – is preferred unless it is also a disadvantage, e.g. B. the slower replication of the virus.

How quickly a particular virus mutates can greatly affect the effectiveness of vaccines, if at all. Influenza viruses swap genes quickly, which is why we need a new vaccine every year. And there is still no vaccine against HIV, the virus that causes AIDS, partly because HIV mutates extremely quickly.

The coronavirus is orders of magnitude less capricious. "There is more viral diversity in a single HIV-infected individual than in the entire world population with covid-19," says Michael Farzan, a biologist at Scripps Research in Jupiter, Florida. "If I found the most diverse versions of SARS-CoV-2, one from China in 2019 and one from Maine in 2020, they would be less different than what you see in a person with HIV."

The coronavirus has a comparatively large genome – around 30,000 letters, three times as many as in HIV or the influenza virus – and it changes much less quickly.

In addition, the spike protein is a fairly large structure made up of around 1,270 amino acids. This offers the body's immune system a broad goal. It makes many different antibodies against different parts of the tip. Moderna and Pfizer / BioNTech vaccines both trigger this “polyspecific” immune response. A single mutation of the spike, or even a few, is not expected to significantly affect the effectiveness of the spike. For example, the British variant contains nine mutations to the spike gene, but is 99% identical to the version that the vaccines can neutralize.

“We know this virus is not stable. No virus is stable. This virus continues to develop, ”said Uğur Şahin, founder and CEO of BioNTech, at a press conference on December 22nd in Germany. "But there are a lot more sites that haven't mutated." Şahin said that every time a new mutation appeared for the past month, the company's laboratory tests showed that the vaccine should continue to be effective. BioNTech has tested about 20 so far and plans to run the same tests on the UK variant. This experiment will take two weeks, but Şahin says that "scientifically very likely" the vaccine is still working.

Similarly, Moderna, who began rolling out its vaccine in the US this week, believed that "vaccine-induced immunity would protect against the variants recently described in the UK". Eli Lilly, who makes an antibody drug against Covid-19, said it had already tested it against the major mutation seen in the UK variant and it is still working.

Keeping up with the coronavirus

However, some researchers say that mutations will ultimately make current vaccines and treatments less effective. “It shows me that we need a different version of the vaccine. I am convinced of that, ”says Farzan. "We will follow these variants like we do the flu."

If updated vaccines are needed, it could greatly favor the technology behind the vaccines from Moderna and Pfizer / BioNTech, both of which are already approved in the US. They use genetic data from the coronavirus in the form of messenger RNA (mRNA) to strengthen the body's immune system. The vaccine is essentially a container with the RNA inside. So when a new variant of the virus emerges, the matching RNA can simply be replaced.

"It is technically possible to manufacture a new vaccine that mimics the new strain in a few weeks," Şahin said at the press conference.

For example, the first doses of the vaccine were made by Moderna last February, just a month after China first disclosed the coronavirus genome.

"That's why people buy stocks in the mRNA companies," says Farzan. "These are the guys who will have the quickest answer on the second run."

What about the drugs?

While companies say vaccines aren't easily affected by some mutations, the two antibody drugs approved so far in the U.S. are less flexible. This is because while a vaccine causes the immune system to make a large number of different antibodies, the antibody drugs consist of only one or two particularly strong antibodies.

At the moment, however, the manufacturers of these drugs are also optimistic.

Bamlanivimab, the drug sold by Eli Lilly, is based on an antibody found in one of the first Covid-19 patients in the United States. The drug is given by injection to people with moderate Covid-19 and was approved in November. Former New Jersey Governor Chris Christie received the drug after catching Covid-19 while U.S. President Donald Trump received similar antibody treatment from Regeneron Pharmaceuticals.

Since the Lilly antibody targets a site in the receptor binding domain, the hot spot on the tip, any mutation in this region – such as the N501Y mutation seen in the UK – could affect the drug's effectiveness. Ajay Nirula, vice president of immunology at Eli Lilly, wrote in an email that the company's tests "suggest that bamlanivimab should retain its full activity against the new strain".

Similarly, Regeneron said it wasn't concerned about the British variant. His treatment involves two antibodies that bind to different parts of the spike protein, making it harder for a random mutation in the virus to deactivate the drug.

"Everything we know so far about this variant and our antibodies – including data from preliminary neutralization analyzes and against other currently circulating variants – shows that our cocktail will remain effective against this new strain," said Alexandra Bowie, spokeswoman for Regeneron.

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Steven Gregory