Researchers say they've possibly discovered just how the SARS-CoV-2 virus is able to spread between people who don't even have symptoms.
The virus behind the COVID-19 pandemic has infected tens of millions of people and killed at least 1.1 million since making the leap to humans in 2019.
The key advantage it has over its predecessor SARS-CoV-1 - the deadly virus behind the 2003 SARS epidemic, which was stopped before it could go global - is that it can spread asymptomatically.
"A crucial feature contributing to the global spread of COVID-19 is that viral shedding starts before the onset of symptoms; in contrast, shedding began two-10 days after the onset of symptoms during the SARS epidemic of 2003," Duke University scientists wrote in a new paper.
"Mutations contributing to viral transmission would likely be favored by natural selection, making tests for positive selection a useful tool for identifying candidate genetic changes responsible for the unique properties of SARS-CoV-2."
You've probably heard of the spike protein - the pointy bits you see in illustrations of the virus, which help it latch onto target cells much better than SARS-CoV-1 ever did.
Comparing the SARS-CoV-1 virus to related coronaviruses in bats and pangolins, the Duke scientists found two other "silent" mutations they believe could be behind the virus' infectivity, dubbed 'Nsp4' and 'Nsp16'.
"Nsp4 and Nsp16 are among the first RNA molecules that are produced when the virus infects a new person," said lead author Alejandro Berrio.
They weren't noticed before because the mutations don't produce proteins. Instead, they appear to affect how the virus folds into different shapes once it's infected a human cell.
Somehow they're giving SARS-CoV-2 a biological advantage, but it's not entirely clear how - it's suspected they help the virus spread before an infected person starts to show symptoms, if they show symptoms at all.
"Scans for positive selection typically focus on changes in protein function and far less often consider the possibility of adaptive change in RNA function.
"By shining a light on regions of the SARS-CoV-2 genome that appear to be under positive selection yet are unlikely to alter protein function, our results illustrate the value of evaluating the potential for adaptive changes in secondary structures within the genomes of RNA viruses."
The discovery could lead the way to new treatments early in an infection that could prevent a serious illness developing.
"The spike protein doesn't get expressed until later," said Dr Berrio, "so they could make a better therapeutic target because they appear earlier in the viral life cycle."
Knowing what kinds of mutations SARS-CoV-2 has compared to its animal-bound relatives will help scientists spot other viruses that could make the leap from animals to humans, the researchers say.
The study was published in journal PeerJ.