From Bats to Human Lungs, the Evolution of a Coronavirus – The New Yorker

There are endless viruses in our midst, made either of RNA or DNA. DNA viruses, which exist in much greater abundance around the planet, are capable of causing systemic diseases that are endemic, latent, and persistentlike the herpes viruses (which includes chicken pox), hepatitis B, and the papilloma viruses that cause cancer. DNA viruses are the ones that live with us and stay with us, Denison said. Theyre lifelong. Retroviruses, like H.I.V., have RNA in their genomes but behave like DNA viruses in the host. RNA viruses, on the other hand, have simpler structures and mutate rapidly. Viruses mutate quickly, and they can retain advantageous traits, Epstein told me. A virus thats more promiscuous, more generalist, that can inhabit and propagate in lots of other hosts ultimately has a better chance of surviving. They also tend to cause epidemicssuch as measles, Ebola, Zika, and a raft of respiratory infections, including influenza and coronaviruses. Paul Turner, a Rachel Carson professor of ecology and evolutionary biology at Yale University, told me, Theyre the ones that surprise us the most and do the most damage.

Scientists discovered the coronavirus family in the nineteen-fifties, while peering through early electron microscopes at samples taken from chickens suffering from infectious bronchitis. The coronaviruss RNA, its genetic code, is swathed in three different kinds of proteins, one of which decorates the viruss surface with mushroom-like spikes, giving the virus the eponymous appearance of a crown. Scientists found other coronaviruses that caused disease in pigs and cows, and then, in the mid-nineteen-sixties, two more that caused a common cold in people. (Later, widespread screening identified two more human coronaviruses, responsible for colds.) These four common-cold viruses might have come, long ago, from animals, but they are now entirely human viruses, responsible for fifteen to thirty per cent of the seasonal colds in a given year. We are their natural reservoir, just as bats are the natural reservoir for hundreds of other coronaviruses. But, since they did not seem to cause severe disease, they were mostly ignored. In 2003, a conference for nidovirales (the taxonomic order under which coronaviruses fall) was nearly cancelled, due to lack of interest. Then SARS emerged, leaping from bats to civets to people.The conference sold out.

SARS is closely related to the new virus we currently face. Whereas common-cold coronaviruses tend to infect only the upper respiratory tract (mainly the nose and throat), making them highly contagious, SARS primarily infects the lower respiratory system (the lungs), and therefore causes a much more lethal disease, with a fatality rate of approximately ten per cent. (MERS, which emerged in Saudi Arabia, in 2012, and was transmitted from bats to camels to people, also caused severe disease in the lower respiratory system, with a thirty-seven per cent fatality rate.) SARS-CoV-2 behaves like a monstrous mutant hybrid of all the human coronaviruses that came before it. It can infect and replicate throughout our airways. Thats why it is so bad, Stanley Perlman, a professor of microbiology and immunology who has been studying coronaviruses for more than three decades, told me. It has the lower-respiratory severity of SARS and MERS coronaviruses, and the transmissibility of cold coronaviruses.

One reason that SARS-CoV-2 may be so versatile, and therefore so successful, has to do with its particular talent for binding and fusing with lung cells. All coronaviruses use their spike proteins to gain entry to human cells, through a complex, multistep process. First, if one imagines the spikes mushroom shape, the cap acts like a molecular key, fitting into our cells locks. Scientists call these locks receptors. In SARS-CoV-2, the cap binds perfectly to a receptor called the ACE-2, which can be found in various parts of the human body, including the lungs and kidney cells. Coronaviruses attack the respiratory system because their ACE-2 receptors are so accessible to the outside world. The virus just hops in, Perlman told me, whereas its not easy to get to the kidney.

While the first SARS virus attached to the ACE-2 receptor, as well, SARS-CoV-2 binds to it ten times more efficiently, Kizzmekia Corbett, the scientific lead of the coronavirus program at the National Institutes of Health Vaccine Research Center, told me. The binding is tighter, which could potentially mean that the beginning of the infection process is just more efficient. SARS-CoV-2 also seems to have a unique ability, which SARS and MERS did not have, to use enzymes from our human tissueincluding one, widely available in our bodies, named furinto sever the spike proteins cap from its stem. Only then can the stem fuse the virus membrane and the human-cell membrane together, allowing the virus to spit its RNA into the cell. According to Lisa Gralinski, an assistant professor in the Department of Epidemiology at the University of North Carolina at Chapel Hill, this supercharged ability to bind to the ACE-2 receptor, and to use human enzymes to activate fusion, could aid a lot in the transmissibility of this new virus and in seeding infections at a higher level.

Once a coronavirus enters a personlodging itself in the upper respiratory system and hijacking the cells hardwareit rapidly replicates. When most RNA viruses replicate themselves in a host, the process is quick and dirty, as they have no proofreading mechanism. This can lead to frequent and random mutations. But the vast majority of those mutations just kill the virus immediately, Andersen told me. Unlike other RNA viruses, however, coronaviruses do have some capacity to check for errors when they replicate. They have an enzyme that actually corrects mistakes, Denison told me.

It was Denisons lab at Vanderbilt that first confirmed, in experiments on live viruses, the existence of this enzyme, which makes coronaviruses, in a sense, cunning mutators. The viruses can remain stable in a host when there is no selective pressure to change, but rapidly evolve when necessary. Each time they leap into a new species, for example, they are able to hastily transform in order to survive in the new environment, with its new physiology and a new immune system to battle. Once the virus is spreading easily within a species, though, its attitude is, Im happy, Im good, no need to change, Denison said. That seems to be playing out now in humans; as SARS-CoV-2 circles the globe, there are slight variations among its strains, but none of them seem to affect the viruss behavior. This is not a virus that is rapidly adapting. Its like the best car in the Indy 500. Its out in front and there is no obstacle in its path. So there is no benefit to changing that car.

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From Bats to Human Lungs, the Evolution of a Coronavirus - The New Yorker