By Lucy van Dorp, UCL
In early January, the first genome sequence of Saras-Kov-2 – the virus that causes Kovid-19, was released under the moniker “Wuhan-1”. This string of 30,000 letters (GS of A, T, C and genetic code) marked a day in the race to understand the genetics of this newly discovered coronavirus. Now, another 100,000 coronavirus viruses sampled from Kovid-19 patients in more than 100 countries have joined Wuhan-1. Geneticists around the world are mining data for answers. Where did Saras-Cove-2 come from? When did it start infecting humans? How does the virus mutate, and does it matter? Sars-CoV-2 genomics, like viruses, grew and went global.
The word mutation combines images of dangerous new viruses with widespread capabilities across the planet. And while mutations constantly arise and occasionally sweep – early mutations in Saras-Cove-2 have made their way around the world as the virus spreads almost unnoticed – the mutation is entirely about any organism, including the virus. Is the natural part of. There is not much effect on the virus’s ability to spread or cause disease.
A mutation means just one difference; A letter change in the genome. While the Sars-CoV-2 population was genetically essentially irreversible when it jumped into its first human host in late 2019, more than 13,000 of these changes are now sequentially found in 100,000 Sars-CoV-2 . Yet anywhere in the world, on any two patients, two viruses differ on average by only 10 letters. This is a small fraction of the total of 30,000 characters in the virus’s genetic code and means that all Sars-CoV-2 in circulation can be considered part of a single clonal lineage.
It will take some time for the virus to gain sufficient genetic diversity. Sars-CoV-2 mutates quite slowly to a virus, with some mutations occurring every month in any lineage; In the same period, the number of mutations received by influenza virus is two to six times less.
Nevertheless, mutation is the basis on which natural selection can function. Most commonly the mutation will present a nonfunctional virus or have no effect. Nevertheless, mutations have the potential to affect the transmission efficiency of SARS-COV-2 in their new human devices. As a result, intensive efforts have been made to determine if a mutation, previously identified since the Saras-Cove-2 genome, was sequenced in Wuhan, which could significantly alter viral function. is.
An infamous mutation in this context is an amino acid mutation in the Saras-COV-2 spike protein, a protein that gives coronaviruses its specific crown-like projections and allows it to attach to host cells. This single characterization change in the viral genome is called D614G – it has been shown to increase the infectivity of viruses in laboratory-developed cells, although there is no measurable effect on disease severity. Although this mutation is found systematically with three other mutations, and all four are now found in approximately 80% of the sequenced Sars-CoV-2 making it the most frequent set of mutations in circulation.
The challenge, along with other mutations with D614G, is unsatisfied as to whether they have increased in frequency as they were present in the viruses responsible for the early successful outbreak seedlings, or whether they actually provide an advantage to their carriers. Although genomics works on UK datasets, suggesting a subtle role of D614G in increasing the growth rate of the lineages it carries, our own work could not find any measurable effect on transmission.
Just took it
D614G is not the only mutation found at high frequency. A string of three mutations in the protein shell of Sars-CoV-2 are also increasingly visible in sequencing data and are now found in a third of viruses. A single change in position 57 of the Orf3a protein, a known immunogenic region, occurs in a quarter. Other mutations are present in spike proteins while innumerable others seem to be stimulated by the activity of our own immune response. At the same time, there is no consensus that these, or any other, are causing significant changes in viral transformation or virility. Most mutations run concurrently as Sars-CoV-2 spreads successfully.
But substitutions are not just small edits that can affect Sars-CoV-2. Lesions in the Sars-CoV-2 secondary genes Orf7b / Orf8 have been shown to reduce virulence of Sars-CoV-2, potentially reducing migraine infections in patients. Similar deletions may have behaved in the same manner as Sal-COV-1, which is responsible for the SARS outbreak in the associated coronovirus 2002–04. Progression to a less sparse Saras-Cove-2 would be welcome news, although the omission in ORF8 has been present since the early days of the epidemic and does not increase in frequency.
While adaptive changes may still occur, at this stage all available data suggest that we have been experiencing the same virus since the onset of the epidemic. Chris Whitty, chief medical officer for England, was right to pour cold water on the idea that the virus muted more than some adulterated mutants, causing Britain to put a lockdown in March. The potential decline in symptom severity seen in summer probably results in younger people becoming infected, measures of infection (such as social differences), and better treatment rather than changes in the virus. However, while the Saras-Cove-2 has not changed significantly to date, we continue to expand our equipment to track and trace its development, ready to keep pace.
Lucy van Dorp, Senior Research Fellow, Microbial Genomics, UCL
This article is republished from chit chat Under a Creative Commons license. Read the original article.
Bottom Line: What science knows about the mutation of the Kovid-19 virus.