The global mutations confounding the fight against Covid have become something of an international sports contest. The British mutation is more infectious, perhaps more lethal and more common in Israel. The South African mutation is also more infectious and perhaps more resistant to the vaccines developed, while little is known about the Brazilian mutation but Brazil has already broken all records. Now the US has weighed in with its own representative, the brand new Californian mutation, which is also probably more infectious.
Are these mutations responsible for the fact that more pregnant women and children are becoming ill with Covid-19, or is it just the spread of the original virus?
Immunologist and virus researcher Prof. Jonathan Gershoni of Tel Aviv University's School of Molecular Cell Biology and Biotechnology in the Life Science Faculty explains that to understand what is happening we must look at the bigger picture. "Beneath the service of this discussion is the question of how we should plan for the future. We have only just begun vaccinating and will all this soon still be relevant? In order to answer this question, we need to delve more deeply into the biology and evolution of viruses."
"First of all we need to understand that the virus does not have a strategic plan. I heard one professional say that after we've vaccinated a high percentage of the adults, the virus will look for new pastures, and we will see it more among children and young people. God forbid! So adults can start thinking that that if they are vaccinated they will cause damage among young people. It is of course utterly wrong."
"If we compare Covid to the weather, it's like saying that when it is raining more heavily, or when the virus spreads more quickly, we will see more people getting wet. But if everybody in the north opens an umbrella that won't divert the rain further south. It is not as though the virus has a daily quota to fill. On the contrary, if the virus comes up against a vaccinated person, it simply won't infect him. If it comes up against a person who is not vaccinated, it will infect him, and then of course that person will go and infect somebody else."
Mutation, says Gershoni, takes place in a completely random way. "Every virus has a mechanism that replicates its RNA, and that mechanism makes errors. During the replication of the coronavirus the errors accumulate with a certain frequency. The more replications that there are, the greater chance of mutations appearing. In other words, the more common that the disease it, the more mutations that are created."
"If a person is vaccinated, the disease won't develop in him but it is possible that he can still be infectious. It is also possible that even if he is infectious, the virus won't replicate with the same efficiency and then the virus caseload will be smaller and a vaccinated person will be less infections than a non-vaccinated person." Therefore, the more that the spread of the virus is slowed down, either by prevention of infection or vaccination, then less mutations will be created.
What happens when there are mutations? "Some of them can cause damage to the virus and those defective viruses won't survive. If for example, there is a mutation that harms the virus's ability to attach to human cells, then the virus cannot replicate. In contrast, there are mutations that will cause the virus to attach with higher efficiency to human receptors. These mutations have an advantage and they will multiply in the population."
Gershoni, who has been researching viral proteins for 30 years, explains that when he thinks of the structure of the spike of the protein and the British mutation, he can say that he has seen it, "The replacement of amino acid asparagines with tyrosine in position 501 is logical, and it is absolutely clear to me that this mutation might improve the connection of the virus to its receptor.
We can really understand the virus down to that resolution?
"Yes. Just as a chef knows exactly what will be the flavor of a dish after adding a sprinkly of cinnamon, so a virus RNA researcher knows the coronavirus in an intimate way and can imagine how this or that mutation will influence the protein spike."
These mutations probably occurred in the past. It's possible that mutations occurred and became more effective in the way they can connect to receptors but that doesn't mean they necessarily became more aggressive. In any case, we must remember that if a person develops this mutation for the first time and he stays in isolation, and doesn't meet anybody, the mutation will disappear as if it had never existed. Only if that person manages to infect other people can it become a dominant mutation."
"In December 2019 in the Chinese city of Wuhan, the virus crossed over the species barrier for the first time and began to infect humans. When the genetic sequence of the virus was published for the first time in January 2020, this sequence represented the virus as it was at the beginning of its adaptation to humans. Pfizer and Moderna based their vaccine on this sequence in the race to develop the first vaccine to halt the pandemic."
Over time, as the number of those infected and sick around the world grew and grew, so the rate of mutations grew and grew. "Consequently, we are witnessing a world cup of mutations currently being reported. It didn't start all of a sudden and it won't end all of a sudden. The virus is randomly checking out every day and all the time the possible mutation space."
But there are places that the virus cannot mutate to without damaging itself because it depends of them to connect with the receptors of human cells. If the virus changes in these places, it loses its ability to transmit. These are also the areas targeted by the antibodies created by the vaccination. In other words the vaccination is programmed to block the critical area where the virus sticks to the receptor.
This is an optimistic point," says Gershoni. "If the virus changes a lot in the places in the places where it attaches to the antibodies of those who have been vaccinated, it is reasonable that it will lose its ability to attach itself well to the receptor. And the virus cannot change, so that it can attack another receptor."
The South African mutation
Against this background, it's possible to check what has caused specific mutations. He said, "In the mutation that we call British there is a change in sequence number 501, which causes it to be more contagious." He dismisses talk that the British mutation could be more lethal as speculative.
The South African mutation has the same change in 501 but in addition there also a change at 417 and mainly there is a change at 484. This is significant because examinations conducted on monoclonal antibodies, in other words very specific antibodies that have been developed to cure Covid, showed that a mutation in the 484 region evades the influence of these antibodies.
However, when we recover from the virus, or when we vaccinate, We don't produce only one type of antibody but a wide range of antibodies that work together to neutralize or reduce the ability of the virus to attach to receptors.
Research into the blood cells of people who have recovered from Covid or have been inoculated with the Pfizer vaccine show that they succeed in neutralizing the British mutation. But what about the South African variant? Here the answers are less clear. In trials conducted on blood of people who have recovered from Covid, a small number succeeded in neutralizing the South African mutation but most didn't. The more antibodies a person has the better the chance to neutralize the South African mutation.
Gershoni explained, "You have to take into account that in these trials, the ability to neutralize the serum is only when it is mixed. It's possible that in unmixed blood, in other words in the body, we would see the vaccination work quite well against the South African mutation."
Trials undertaken by both Pfizer and Moderna on people eight weeks after the second dose have shown almost full protection against the South African variant. There are currently only several dozen cases of the South African mutation in Israel, so if everybody infected remains in isolation, socially distanced or wears masks (properly) it will disappear from Israel.
Published by Globes, Israel business news - en.globes.co.il - on January 25, 2021
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