A new viral cousin of Covid-19 may resist vaccine immunity, study finds

There are more viruses on planet Earth that there are no stars in the universe. According to a 2011 estimate, if we gathered all these microbes (from ten to the 31st power, or 10 billion million) and lined them up end to end, we would form a microscopic highway stretching 100 million light years.

Sounds amazing, right? Or maybe a little scary considering viruses aren’t exactly known for their sunny disposition. For the most part, these microorganisms are very selective in how or who they infect; only a fraction of people in the environment pose a threat to humans, whether serious or not. But as the recent Covid-19 pandemic has taught us, viral outbreaks do happen. That’s why virologists around the world are working hard to discover and characterize these insidious microbes before they make us their unwitting hosts.

To that end, a group of researchers at Washington State University has discovered that coronaviruses distantly related to SARS-CoV-2, the pathogen behind Covid-19, are resistant to our vaccines and monoclonal antibody therapies current, according to a study published Thursday in the newspaper PLOS Pathogens. Called Khosta-2, these viruses use the same cellular port of entry as SARS-CoV-2 and, given the right circumstances, could transform into something much more pathogenic than they are right now, as we’ve seen with the new Covid. -19 variants.

“Since these viruses exist in nature, [these findings] It really drives home the point that we should create more active vaccines” that target all members of the coronavirus family, said Timothy Sheahan, a virologist at the University of North Carolina’s Gillings School of Global Public Health, who was not involved in the study, he says reverse.

Bats are believed to be the main animal reservoir of coronavirus worldwide.image alliance/image alliance/Getty Images

Here’s the bottom line – As we are probably all too familiar with, coronaviruses are a large family of viruses that cause respiratory and intestinal diseases in both humans and animals, and have been circulating for a long time. In recent years, scientists created a new term, sarbecovirus, to differentiate those coronaviruses genetically related to SARS-CoV-1, the virus behind the 2002 outbreak of severe acute respiratory syndrome first identified in Guangdong, China . These include SARS-CoV-2 and hundreds of strains that infect animals such as civets, pangolins and bats, which are considered the main reservoir.

Russian horseshoe bats are where scientists found Khosta-2 and a closely related Khosta-1 in fecal and oral samples taken in late 2020 near Sochi National Park. Further analysis of this particular strain showed that its genome shares strong similarities with sarbecoviruses found in horseshoe bat samples collected in Bulgaria in 2008 and Kenya in 2007. Although hundreds of sarbecoviruses tested so far have not shown no ability to infect human cells, initial studies found that Khosta viruses have structural components that may allow them to interact with ACE2, or angiotensin-converting enzyme 2, a protein in human cells to which the spike protein of the virus attaches itself to enter. It is the same lock and key mechanism that SARS-CoV-2 uses.

What they did – Led by Washington State University virologist Michael Letko, the researchers created viral pseudotypes. These are viral particles made from a benign virus that has been edited to carry the full-length SARS-CoV-2 spike protein, although the protein has been modified to carry the receptor-binding domain (RBD) of Khosta instead of SARS-CoV-2. . (The RBD is the part of the spike protein that interacts with ACE2.)

It’s a similar approach that Letko used in 2020 to characterize the SARS-CoV-2 receptor. In this case, viral particles carrying the Khosta RBD were mixed with human and animal cells coated with human ACE2. Letko and colleagues saw that Khosta viral particles, especially those loaded with the Khosta-2 RBD, bind ACE2 readily with about the same avidity as SARS-CoV-2 viral particles. (The comparison included RBD-containing viral particles from more than 30 other sarbecoviruses, including the original Wuhan and Omicron SARS-CoV-2 variants.)

The spike protein of the coronavirus (depicted in red) enters cells through ACE2 (depicted in blue). Shutterstock

Next, the researchers wanted to assess how well our current immune arsenal, namely antibody therapies and Covid-19 vaccines, stacked up against Khosta viruses. The results were troubling: Khosta’s viral particles, again those with Khosta-2 RBDs, appeared to be completely resistant to Bamlanivimab, a monoclonal antibody therapy approved with emergency use authorization in November 2020 to treat variants prior to Covid-19.

Vaccines fared no better. Letko and his team incubated Khosta-2 in serum from people vaccinated with the earlier shots from Moderna and Pfizer, as well as from people who recovered from the Omicron strain. While SARS-CoV-2 viral particles were easily retained by the antibodies present, Khosta-2 was completely resistant. However, this is not entirely surprising: Khosta-2 is a different virus from SARS-CoV-2, and its spike protein shares only about 60 percent similarity with other sarbecoviruses, including SARS-CoV-2 .

Why does it matter – Before you panic, Khosta-2 is not the next viral villain, at least not anytime soon. The virus appears to have no genes that cause disease in humans. But Letko says the fear lies in recombination when two or more viruses co-infect the same host and exchange genetic information like a genomic sale.

“The real fear is that if you get a recombination between something like SARS-2 and Khosta-2 because then it can have all the properties of SARS-2 [like] pathogenesis, but may have a different receptor binding domain that makes it resistant to the [Covid-19] vaccines,” Letko tells reverse.

Letko and Sheahan stress that recombination doesn’t necessarily have to result in a more pathogenic virus (Khosta-2 can never gain the ability to infect humans), but it’s a possibility nonetheless, especially if the two are in a animal host before jumping into it. human beings.

“Our biggest concern is the diversity there is and the fact that we can now accidentally introduce a pathogenic virus like SARS-2 into this pool of other viruses,” says Letko.

Antiviral drugs like Paxlovid and remdesivir could protect us from any future outbreaks of sarbecovirus. Shutterstock

Although studies show that climate change could accelerate the chances of this potentially disastrous viral encounter for all viruses (not just Khosta-2 and SARS-CoV-2), we are not completely helpless. Sheahan and Letko say scientists are working on a universal sarbecovirus vaccine that would offer protection not only against SARS-CoV-2 variants, but also against many other animal-derived coronaviruses that seek to harm us. Antiviral drugs such as Remdesivir and Paxlovid, both currently prescribed for Covid-19, could also offer great protection and defense.

“Antiviral drugs act on slightly broader mechanisms than just [targeting] the spike protein,” Letko says. “They’re acting on something a little more conservative and more similar between these viruses. So hopefully you’d have more of a fighting shot with something like that.”

What follows – For Letko, encountering Khosta-2 and investigating its secrets is part of a larger research effort to characterize all sarbecoviruses and see how well (or not) these microbes can infect us.

“We’ve covered a pretty wide range of everything Mother Nature can produce with sarbecovirus,” he says. “The idea is to keep building this information so that we can put it into a big database … so that when a new virus is discovered, we don’t always have to test it in a lab or isolate it.”

Just as, during the pandemic, scientists were able to develop vaccines quickly, in part thanks to the rapid knowledge of the genetic sequence of SARS-CoV-2, Letko hopes that a virtual library of sarbecoviruses will prepare us if we are ever faced with another viral outbreak. .

“When the next one comes in, we’ll say, ‘Oh, we’ve seen this sequence data before, we’ll see what we can go with,'” Letko says.

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