Origin of SARS-CoV-2 | 2021-05-13 | BioWorld

About a year and a half after the COVID-19 pandemic began, many uncertainties remain about the future of the virus. Whether it changes, how long the protection from the disease or vaccination lasts, when it is no longer a pandemic and instead becomes endemic, whether the worst is still ahead. There is also growing recognition that there are still unclear points about the past of SARS-CoV-2.

Specifically, there is growing question as to whether the pandemic began with the spread of zoonotic diseases from wildlife, or whether it escaped from the laboratory with a twist of fate.

Currently, both of these two origins are possible. In a letter issued May 13, 2021 Science, A group of researchers frankly entitled “Investigating the Origin of COVID-19,” said: Knowing how COVID-19 emerged is important to inform global strategies to mitigate the risk of future outbreaks. “

And at a Senate hearing on COVID-19 on May 11, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, admitted that an accidental escape of SARS-CoV-2 was “potential.” I did.

Fauci expressed support for further investigation into whether SARS-CoV-2 originated from a coronavirus study conducted at the Wuhan Institute of Virology. But he said, “I don’t know if we can prove the origin of SARS-CoV-2.”

Even the question of what it means for the virus to come from the laboratory, Stanley Perlman said. BioWorld, “It turned out to be more complicated than I imagined.”

Perlman is a professor of pediatrics, a professor of microbiology and immunology, and chairman of Mark Stinski of virology at the University of Iowa’s Carver Medical College. He has been studying coronavirus since 1982.

As an extreme example, you can imagine that the proverbial mad scientist can take publicly available information and use it to create a virus from scratch. That possibility can probably be safely discounted, according to Perlman, as it may not actually work.

On the other hand, if a researcher collects the virus from bats that are already adapted to humans and someone unknowingly infects the outside world, “it’s very difficult to rule out that scenario,” he said. Said.

The potential for the most political attention is intermediate. Researchers have collected the virus from bats and manipulated it to make it more contagious among humans and then let it escape.

SARS-CoV-2 has several features that are compatible with its potential. This virus has cleavage sites that are not found in other known coronaviruses but allow cleavage by the human protein furin, which is present in laboratory-operated coronaviruses. The SARS-CoV-2 genome also contains codons for the amino acid arginine, which is more commonly used by humans than viruses.

However, while the characteristics of these molecules are consistent with lab operations, they are not a sure sign.

According to Perlman, for example, about half of the murine hepatitis viruses have furin cleavage sites, and the other half do not. Perhaps other as yet unknown coronaviruses also have furin cleavage sites.

“When we make recombinant viruses, we are trying to understand what the virus does … almost everything we do attenuates the virus,” or less infectious. “This is normal for these methods to work.”

Continuous passage, the fastest way to mutate a virus that leaves no apparent molecular signs of manipulation, is usually more infectious to cells, but less infectious in the more complex environments of humans and animals. Brings a virus.

In the wild, when it comes to pandemic pathogens, SARS-CoV-2 took about a year and millions of infections to evolve a significantly more infectious mutant.

No smoking gun

Perlman said some of the problems were “there’s so little data that they’re actually pointing to one or the other … which makes it a little more likely to be very unlikely.” ..

The most important hole in the zoonotic spillover theory is that no SARS-CoV-2 reservoir has been identified in either the bat colony or intermediate host near Wuhan.

“We can’t find anything bloody anywhere,” Perlman said.

In contrast, camels in 15 months during a much smaller outbreak that took 4 months to identify civet as an intermediate host for SARS-CoV-1 and did not order some of the research attention of the COVID-19 pandemic. I found. As an intermediate host for MERS-CoV.

Identifying a natural reservoir would be a smoke gun for the zoonotic spillover hypothesis.

Paradoxically, the lab escape hypothesis is difficult to prove and difficult to disprove.

To prove your escape from the lab, you need to find the virus in the lab. “It’s possible that someone in these political eras would really open up their lab … it’s hard to imagine it ever happening,” Perlman said. “And even if that happens, it’s almost impossible to prove negative.”

The debate about the origin of SARS-CoV-2 is taking place in the larger context of a highly political climate, and is freely accessible and neutral to those who are convinced of the laboratory escape (or liberation) hypothesis. Even if an inspector appears, it is unlikely that he will change his mind. Empty-handed.

Indeed, even viruses with natural reservoirs could theoretically escape or be released, so identifying wild reservoirs is more of a belief in laboratory escape than scientific. You cannot always be sure that it is political.

Whether the virus spills from wildlife or escapes from the laboratory, the key to a pandemic is the ability to replicate with the nose, facilitating human-to-human transmission through casual contact.

In contrast, MERS-CoV is transmitted predominantly in hospitals from person to person, and SARS-CoV-1 spreads through close contact within the home, causing global disruption of SARS-CoV-2. I can no longer do it.

After all, the problem of laboratory escape and zoonoses “partially obscures the most important things … the point is that it comes from bats and eventually becomes a population. I want to know how it happened. “