This area of ​​the Covid-19 virus is one we cannot ignore

Random differentiation is an essential part of all living things. It drives diversity, which is why there are so many different species. There are no viruses. Most viruses are known to modify genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, is not only changing, but changing in ways that are important. This is the thirteenth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, and part twelve.

In my last two articles, I went over the case studies of London and Boston patients. Both were immune and infectious with Covid-19. Both, in the samples of SARS-CoV-2 taken from their bodies by researchers, also contained mutations that arose independently, but were identical to those observed. in new versions of the virus – a phenomenon previously recorded by Jesse Bloom and his colleagues in the flu virus. These and many similar issues, I said, open a window into what this virus has for us.

Which brings me to my next topic, a man I call a Pittsburgh patient, whose story was documented in a study published in Science magazine earlier in the month. Prior to the positive diagnosis of Covid-19, this patient was undergoing treatment for cancer and, the authors of the study note, has already been vaccinated. The Pittsburgh patient suffered a severe Covid-19 rash for about two and a half months before he contracted the disease.

Like London and Boston patients, while in hospital the Pittsburgh patient underwent a series of experimental tests, including the steroid dexamethasone, the antiviral drug remdesivir, and two rounds of convalescent serum, or preparation of highly neutral antibodies collected from recovered Covid-19 patients (Figure 1). These treatments put pressure on the virus to develop – and evolve as it did, but in ways that transcend issues from other patients with chronic infection. What remained stable in all three, however, was that these mutations appeared to have some sort of benefit to SARS-CoV-2, or would not have lasted as long.

Most of the notable mutations in London and Boston patients occurred in the spike protein receptor binding domain, the target for many drugs and vaccines, as well as the furin acting site. Almost all of them were point mutations, changes that affected only one amino acid at a time, with the exception of a few deletions. This was not true for a Pittsburgh patient, who had much more deletions in their viral genomes than any other type of mutation. Moreover, the majority were concentrated in the N-terminal range: Δ69–70, Δ141–144, Δ144–145, Δ146, Δ210, and Δ243–44 (Figures 2, 3, 4). . If there were mutations in other areas of the virus, they were not clearly reported in the study.

The lack of mutations in the receptor binding field makes Pittsburgh a very advanced patient. But the end result is – the virus lasts much longer than usual. Most of the negative consequences we have had for the new SARS-CoV-2 variants – increased transmission, immune deficiency and so on – we trace back to point mutations located in the receptor binding range. But these changes have changes in the N-terminal range that we would be willing to overlook.

The Pittsburgh patient data certainly suggests that we should pay far more attention to eradication and wider N-terminal land as influencers of change, especially when it comes to how the virus interacts with the immune system and vice versa. Several laboratory experiments have shown that a combination of mutations in the N-terminal range creates resistance to the effects of convalescent serum. The overall role of this global segment of SARS-CoV-2 may not be known, but I have thought that, based on its specific shape, the new variables could either increase relationship as the second receptor or elimination of antigenic sites where monoclonal antibodies bind.

Some of the deletions have been reported in Pittsburgh patients we have seen before, both at the individual and population level. Δ69-70, for example, is present in the UK version, B.1.1.7, while Δ243-244 is a feature of the B.1.153 version in South Africa. Not to mention Δ141-146 is almost the same as eliminating detection in Boston patients. When Kevin McCarthy, the lead researcher behind the Pittsburgh patient study, cross-referenced this data with GISAID data, a genome sequence database for SARS-CoV-2 and the flu, he discovered that of the viruses. all with the elimination of the S protein, 90 percent of the deletions occurred at one of four sites in the N-terminal domain. This means that deletions in McCarthy’s study were common in genomes that were followed worldwide.

The case of the Pittsburgh patient makes one thing clear. If we do not pay attention to mutations that occur throughout the entire spectrum of the SARS-CoV-2 genome, there is a risk that we will miss a piece of the puzzle that may be important for future variants. My next piece in this series will be about another Covid-19 patient with a chronic disease and what those we see in nature might expect: the Italian patient.

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