SARS-CoV-2 Could Evade Some Antibody Therapies: Study
Tue, April 20, 2021

SARS-CoV-2 Could Evade Some Antibody Therapies: Study


A team of researchers discovered that mutations in the spike protein of SARS-CoV-2 could render some treatments ineffective. However, a combination of antibody therapies could overcome the problem if it occurs in real life.

The investigation of mutations in the spike protein of the coronavirus was led by Rockefeller University. These mutations were simulated in different viruses in the lab setting. With sufficient external influence, the spike proteins of SARS-CoV-2 could mutate and evade select treatments. But researchers said that the chances of it happening in real life is extremely low. They published their findings in the journal bioRxiv.

Evolution and Mutation of Viruses

Despite not being entirely alive, viruses are capable of evolution and mutation. Alone, these microorganisms are dormant as if in stasis. But once in contact with cells, viruses may be awakened and start an infection. For biologists, viruses are not living organisms and are likely a resemblance to androids. This is because they are not composed of cells, cannot grow, and cannot generate their own energy.

According to Khan Academy, an American nonprofit educational organization, viruses can become diverse via evolution and mutation. These two factors are crucial when it comes to human-infecting viruses, such as influenza, HIV, and SARS-CoV-2 of COVID-19. While some viruses evolve and mutate at a slow pace, others do at a faster rate. The fast evolution and mutate rates can make it difficult to treat viral infections.

Viruses can grow by infecting host cells. Though, host cells are defined through natural selection. Bacteriophages, for instance, only infect bacteria and each viral strain only infects a particular bacterial strain. If two viruses infected a cell simultaneously, they may share genetic materials that often result in mixed viruses. This is how different strains of a virus are created like influenza strains. But among viruses, RNA variants like HIV have the fastest mutation rates.

Inside a host, viruses can evolve quickly and it affects their infectivity and resistance to medication. Sometimes, they can evolve faster than their host. Recombination or the swapping of the genetic material between viruses is the primary factor of evolution. But in mutation, the alteration in the genetic material occurs during replication.

Similar to cells, viruses can encounter errors when replicating. Significant errors can lead to substantial mutations. Mutations can either be favorable or unfavorable for viruses. Unfavorable mutations make the pathogen more susceptible to treatment or other external effects. But mutations are commonly fixed by viruses via DNA polymerases from host cells. These are the proofreaders of the replication process to ensure no errors happen.



SARS-CoV-2 Mutations Could Be Problematic

Recently, a team led by Rockefeller University examined the mutations in SARS-CoV-2 and their relationship with upcoming treatments and vaccines. They found that some treatments might be rendered useless. Those treatments based on antibody approaches could be dodged by the virus. With mutated spike proteins, the antibodies could not lock and disable the virus due to imperfect fit.

"These are the mutations that are potentially problematic," said Dr. Paul Bieniasz, a lead author of the study and virologist at Rockefeller, quoted American newspaper The New York Times.

In the study, researchers highlighted the current approach of most treatment and vaccine studies: to protect populations from SARS-CoV-2. The best method is to exploit antibodies since the pathogen is a virus. By delivering or inducing antibodies, a person will have the armaments to stop or fight the virus. This is especially useful in protecting healthcare workers and the global healthcare sector.

Researchers examined the spike protein of the virus. It is both the strength and weakness of SARS-CoV-2. If a method could disable it, it would prevent infection in people. So, they utilized different viruses for a series of experiments. Next, they engineered the spike protein into the viruses to have synthetic samples in the lab. Then, they applied antibodies and healthy cells to simulate an environment.

Different antibodies were used to disable the synthetic viruses. Some of them were successfully stopped by antibodies. However, others managed to elude the attack and infect healthy cells. The survivors effectively replicated inside infected cells. Analyses done on surviving viruses revealed the influence of mutations in the spike protein. Though, researchers said the public should not be alarmed.



Based on sequencing performed on SARS-CoV-2 samples collected worldwide, some of those mutations are in human circulation. But the alterations are only found in less than 0.1% of sequences. More than 99.9% of the sequences remain viable for treatments and vaccines. Moreover, the anomalies identified were no more predominant than those with other genetic backgrounds, according to structural biologist Christopher Barnes, who collaborated with researchers.

Barnes explained that the proofreading part of SARS-CoV-2 may lower the odds of those mutations in real-world settings. As mentioned earlier, the virus attempts to correct any possible errors in its replication process. Otherwise, the errors may lead to mutations including anomalies that can stop stable copies.

The findings simply showed the theoretical scenario of spike protein mutations. Researchers pointed out that sufficient external pressure can induce altered spikes. For example, if hundreds of thousands of people are treated with the same antibody therapy, they may assist the distribution of resistance. Some patients may develop resistant SARS-CoV-2 and it can be passed to others. It is comparable to antibiotic-resistant bacteria.

Fortunately, a combination of two or more antibody therapies can overcome the problem. In HIV treatment, a patient may be prescribed with up to five antiretrovirals to counter a resistant strain. This is applicable in resistant SARS-CoV-2.

According to Statista, a German portal for statistics, the mortality rate of COVID-19 is higher than SARS. In the data released on February 10, 2020, by Johns Hopkins University and the US CDC, the cases of COVID-19 worldwide was at 40,561, compared to the 8,096 of SARS. The cases of death due to the disease was at 910, greater than the 774 of SARS.

In terms of infection rate, SARS had a rate of three in both low and high estimates. While COVID-19 had a rate of between 1.5 and 3.5, as of March 6, 2020. Other viruses like Ebola had a rate of between 1.5 and 2.5, MERS from 0.42 to 0.92, and seasonal influenza at 1.3 in both estimates.

The chances of SARS-CoV-2 to evolve within several mutations at once is extremely small. That gives enough room for scientists to seize the virus.