Variants of SARS-CoV-2 Variants Emerge in Brazil

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The unchecked spread of the more contagious SARS-CoV-2 variants in Brazil appears to have created even more dangerous versions of the virus that causes COVID-19.

The changes are documented by a team of researchers from FIOCRUZ, a large public health research lab run by Brazil’s Ministry of Health. 

The findings were recently posted in a preprint on Virological.org, ahead of peer review.

The study describes 11 SARS-CoV-2 sequences from five different Brazilian states.  Each had telltale changes to the receptor binding domain, making it one of the known variants of concern or variants of interest. Each one also had additional changes to another important region on the virus: the N-terminal domain.

The N-terminal domain changes were deletions of important antibody-binding sites.  Many of these were key deletions around Y144, a mutation that has arisen independently in other circulating variants and has been documented in viral mutations in convalescent patients with cancer, suggesting that it conveys an important advantage to the virus.

Modeling by the FIOCRUZ team suggests the deletions will further disrupt the ability of antibodies to grab the virus and prevent them from infecting cells.

“These findings highlight the urgent need to address the SARS-CoV-2 vaccines’ efficacy toward those emergent SARS-CoV-2 variants and the risk of ongoing uncontrolled community transmission of SARS-CoV-2 in Brazil for the generation of more transmissible variants,” the study authors write.

Need to “Shut Down Replication”

Brazil is in the midst of another devastating wave of COVID-19 infections, fueled by variants and political inaction. Hospitals have run out of beds and other key supplies, like ventilators and oxygen, and Brazilian president Jair Bolsonaro has balked at the idea of asking citizens to wear masks and refuses to implement lockdowns, saying the price to the country’s economy would be too high.

Researchers who were not involved in the study said the findings should put the rest of the world on alert.

John Mellors, MD, chief of infectious diseases at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, said the finding was “not surprising, but concerning.”

Mellors and his colleagues were part of a team of researchers who documented one of the same changes — a deletion at position 144 of the N-terminal domain — in a patient with patient who fought the virus for more than 2 months. 

Over time, genome sequencing revealed that the patient, who was treated with convalescent plasma and the antiviral drug remdesivir to try to boost his immune response, was the host of at least six different SARS-CoV-2 variants. The variants had many of the mutations that are carried by the variants of concern that have arisen in the United Kingdom, South Africa, and Brazil.

The N-terminal domain deletions documented in the new preprint have been detected in other parts of the world as well.

“The fact that the same deletions are being selected for, independently of one another, it really suggests that these domains are really important for antibody neutralization,” said Kevin McCormick, PhD, a postdoctoral researcher in infectious disease at the University of Pittsburgh School of Medicine.

A separate study, published earlier this month in the journal Science, found that deletions at position 144 disrupt the binding of antibody 48A.

In response to infection or a vaccine, our bodies make a whole orchestra of y-shaped antibodies that are each designed to grab onto a virus in slightly different places. So losing one of these antibody docking sites on the virus, by itself, isn’t necessarily cause for alarm. But the more the SARS-CoV-2 shape shifts and changes, the more our immune defenses lose their collective punch, and eventually the changes allow the virus to cause a reinfection or to defeat the protection created by a vaccine.

Right now, according to the Centers for Disease Control and Prevention, which is tracking the variants, there are no virus variants that cause tests, vaccines, or treatments to fail completely.

“The biggest move we all need to make is to vaccinate as far and wide as we possibly can to prevent the virus from replicating,” said Mellors. “No replication, no evolution. So if we shut down replication and spread, we’ll be OK, and that’s a huge, enormous undertaking across the globe to shut it down.”

Sources:

John Mellors, MD, chief of infectious diseases, at the University of Pittsburgh School of Medicine, Pittsburgh, PA

Virological.org. Published March 18, 2021. Preprint

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