Amazing Science

A study involving more than 5,000 COVID-19 patients in Houston finds that the virus that causes the disease is accumulating genetic mutations, one of which may have made it more contagious. According to the paper published in the peer-reviewed journal mBIO, that mutation, called D614G, is located in the spike protein that pries open our cells for viral entry. It’s the largest peer-reviewed study of SARS-CoV-2 genome sequences in one metropolitan region of the U.S. to date.

The paper shows “the virus is mutating due to a combination of neutral drift — which just means random genetic changes that don’t help or hurt the virus — and pressure from our immune systems,” said Ilya Finkelstein, associate professor of molecular biosciences at The University of Texas at Austin and co-author of the study. The study was carried out by scientists at Houston Methodist Hospital, UT Austin and elsewhere.

During the initial wave of the pandemic, 71% of the novel coronaviruses identified in patients in Houston had this mutation. When the second wave of the outbreak hit Houston during the summer, this variant had leaped to 99.9% prevalence. This mirrors a trend observed around the world. A study published in July based on more than 28,000 genome sequences found that variants carrying the D614G mutation became the globally dominant form of SARS-CoV-2 in about a month. SARS-CoV-2 is the coronavirus that causes COVID-19. So why did strains containing this mutation outcompete those that didn’t have it?

Perhaps they’re more contagious. A study of more than 25,000 genome sequences in the U.K. found that viruses with the mutation tended to transmit slightly faster than those without it and caused larger clusters of infections. Natural selection would favor strains of the virus that transmit more easily. But not all scientists are convinced. Some have suggested another explanation, called “founder’s effects.” In that scenario, the D614G mutation might have been more common in the first viruses to arrive in Europe and North America, essentially giving them a head start on other strains.

The virus SARS coronavirus 2 (SARS-CoV-2) is the known cause of coronavirus disease 2019 (COVID-19). The "spike" or S protein facilitates viral entry into host cells.

Now a group of researchers from Seoul National University in South Korea, University of Cambridge in UK, and Lehigh University in USA, have worked together to produce the first open-source all-atom models of a full-length S protein. The researchers say this is of particular importance because the S protein plays a central role in viral entry into cells, making it a main target for vaccine and antiviral drug development.

The details can be found in a paper , "Developing a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein Model in a Viral Membrane" just published online in The Journal of Physical Chemistry B.

This video demo illustrates how to build this membrane system from their SARS-CoV-2 S protein models. The model-building program is open access and can be found from the home page of CHARMM-GUI by clicking on the COVID-19 Archive link , or by clicking the archive link in the header, then the COVID-19 Proteins link in the left sidebar.

COVID-19 Symptoms Swayed By Genetics

More info from WIRED Magazine

Some people experience Covid-19 as nothing more than a mild cold, and others exhibit no symptoms at all. Then there are the thousands who sicken and, often, die. Scientists are working hard to understand the underlying reasons for such huge discrepancies in symptoms and outcomes. No one knows the answer yet. One theory: It is locked deep in our genetic makeup.

Humans are not the only species facing a potential threat from SARS-CoV-2, the novel coronavirus that causes COVID-19, according to a new study from the University of California, Davis.

An international team of scientists used genomic analysis to compare the main cellular receptor for the virus in humans -- angiotensin converting enzyme-2, or ACE2 -- in 410 different species of vertebrates, including birds, fish, amphibians, reptiles and mammals.

Research could be a crucial step in helping scientists develop approaches to predict severity of future coronavirus disease outbreaks.

A team of researchers from the National Library of Medicine (NLM), part of the National Institutes of Health, identified genomic features of SARS-CoV-2, the virus that causes COVID-19, and other high-fatality coronaviruses that distinguish them from other members of the coronavirus family. This research could be a crucial step in helping scientists develop approaches to predict, by genome analysis alone, the severity of future coronavirus disease outbreaks and detect animal coronaviruses that have the potential to infect humans. The findings were published this week in the Proceedings of the National Academy of Sciences(link is external).

COVID-19, an unprecedented public health emergency, has now claimed more than 380,000 lives worldwide. This crisis prompts an urgent need to understand the evolutionary history and genomic features that contribute to the rampant spread of SARS-CoV-2. “In this work, we set out to identify genomic features unique to those coronaviruses that cause severe disease in humans,” said Dr. Eugene Koonin, an NIH Distinguished Investigator in the intramural research program of NLM’s National Center for Biotechnology Information, and the lead author of the study. “We were able to identify several features that are not found in less virulent coronaviruses and that could be relevant for pathogenicity in humans. The actual demonstration of the relevance of these findings will come from direct experiments that are currently getting under way.”

Using integrated comparative genomics and machine learning techniques, the researchers compared the genome of the SARS-CoV-2 virus against the genomes of other members of the coronavirus family and identified protein features that are unique to SARS-CoV-2 and two other coronavirus strains with high fatality rates, SARS-CoV and MERS-CoV. The identified features correspond with the high fatality rate of these coronaviruses, as well as their ability to move from animal to human hosts.

These features include insertions of specific stretches of amino acids into two virus proteins, the nucleocapsid and the spike.

These features are found in all three high-fatality coronaviruses and their closest relatives that infect animals, such as bats, but not in four other human coronaviruses that cause non-fatal disease. In particular, the insertions in the spike protein are predicted, from protein structure analysis, to facilitate the recognition of the coronavirus receptors on human cells and the subsequent penetration of the virus into those cells. Finding these features in animal coronavirus isolates could predict the jump to humans and the severity of disease caused by such isolates.

The virus has mutated. But that doesn’t mean it’s getting deadlier.

At this point in the pandemic, coronavirus genomes with 10 or fewer mutations are common, and only a small number have over 20 mutations — which is still less than a tenth of a percent of the genome.

Over time, viruses can evolve into new strains — in other words, viral lineages that are significantly different from each other. Since January, researchers have sequenced many thousands of SARS-CoV-2 genomes and tracked all the mutations that have arisen. So far, they haven’t found compelling evidence that the mutations have had a significant change in how the virus affects us.