Almost immediately after the outbreak emerged, researchers began looking for patterns of change among the tens of thousands of viral genome sequences of SARS-CoV-2. The search was made possible thanks to the willingness of researchers around the world to upload their data to a common database. The data is open source, meaning anyone with a computer can access and analyze the data.
The alert that a change in the genome of SARS-CoV-2 was afoot first emerged from researchers skilled in the art of deciphering the messages encoded in the genome of HIV-1, the virus that causes AIDS. The ability to find meaning in over one billion bits of such information has been honed by decades of research on the ever-changing genomes of HIV-1, which can make a life or death difference in how the virus responds to antiviral drugs. Once you know the tale the genomes tell, you can choose which drugs to use to treat a specific strain of the virus.
The researchers studying the SARS-CoV-2 genome first noticed that one mutation, known as D614G, dominated all others. It first appeared in February as a rare variant in Europe, before spreading and overtaking other strains in Italy and other countries. The research team quickly identified a single change in the virus genome. The mutation affects the spike protein on the outer surface of the virus, for which the coronavirus is named (the Latin word corona means “crown” or “halo”). The spike is of special importance in the life of the virus, since it is the mechanism that allows the virus to recognize and attach itself to a host cell before infecting it. The original authors speculated that the change improves the ability of the virus to stick tightly to mucous membranes in the nose or eyes to begin the process of infection.
The original report was met with skepticism. Some asked whether the dominance of this new strain was the result of an unrelated phenomenon. Given that the researchers had been relying only on publicly available data and computer analyses of the genome, they were unable to definitively conclude that their idea was the only reasonable explanation for the emergence of the new dominant strain.
Until now.
The Scripps Research Institute in Florida answered this question in an unreviewed research manuscript published Friday. The researchers used an elegant set of methods to show that one small mutation stabilized the spike protein, which typically sheds from the surface of the virus. “The mutation had the effect of markedly increasing the number of functional spikes on the viral surface,” senior author Hyeryun Choe said. “The number — or density — of functional spikes on the virus is 4 or 5 times greater due to this mutation.” The result: Each mutant virus particle has an increased ability to infect target cells.
This study clearly shows the virus is evolving. It also found the mutation was nearly 10 times more infectious in a laboratory setting than other strains. With genomic analyses showing that this strain has become the dominant one, the findings could explain why the novel coronavirus has spread so widely in Europe, the United States and Latin America.
Does more transmissible mean the strain is more lethal? Not that we can observe, as of now. From the perspective of the virus and its capacity for survival, it is better to allow those who have been infected to live and spread the virus, rather than die.
Is this the end of SARS-CoV-2’s evolution? Not by a long shot. Doctors in northeastern China have noted that patients in a new cluster of cases appear to carry the virus for a longer period of time and take longer to test negative. They also found that patients were taking longer to show symptoms after infection. The virus could be mutating to become more persistent as another way to survive, since those who carry the virus for a longer period have more opportunities to infect others. Understanding the biochemical basis for this change will be fascinating.
Last month a pair of manuscripts examined variants in one of the SARS-CoV-2 proteins, specified by the orf3b gene, which suppresses part of our immune response to virus infections. One particular variant of orf3b does so more effectively than the original, which may give the virus more time to replicate in the absence of an effective immune response. A sicker patient may be the result.
As of this week, SARS-CoV-2 has infected more than 7.6 million people. That’s remarkable for a virus that very likely began with the infection of a single person roughly six months ago. SARS-CoV-2 has now had seven million more chances to adapt to its new human ecosystem, and there are hints that the virus is doing a good job of it.
We know from our experience with many viruses like HIV-1 and influenza, that we are not facing a static foe. The novel coronavirus is changing, as we struggle to control the pandemic. SARS-CoV-2 has already proven to be a formidable adversary. While our success today — though arguably limited — is important, we should not lose sight of the long battle against microbe that lies ahead.
