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Thread: Coronavirus with an R0 of 3 or beyond

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    Source: University of Helsinki




    An artistic representation of how the coronavirus protein 'spike' (in red) could bind to the cellular receptor ACE2 (dark green) and to the newly identified receptor Neuropilin-1 (light blue) on the surface of cells (yellow).



    Open Sesame! Researchers discovered the second ‘key’ used by the SARS-CoV-2 virus to enter human cells



    To efficiently infect human cells, SARS-CoV-2, the virus that causes COVID-19, is able to use a receptor called Neuropilin-1, which is very abundant in many human tissues including the respiratory tract, blood vessels and neurons. The breakthrough discovery was made by a German-Finnish team of researchers led by neuroscientists Mika Simons, Technical University of Munich, Germany and virologist Giuseppe Balistreri, Faculty of Biological and Environmental Sciences, University of Helsinki, Finland.

    Why is the new coronavirus so infectious?

    “That SARS-CoV-2 uses the receptor ACE2 to infect our cells was known, but viruses often use multiple factors to maximize their infectious potential” says Dr. Giuseppe Balistreri, head of the research group Viral Cell Biology at the Faculty of Biological and Environmental Sciences, University of Helsinki involved in the study. “Unlike the main receptor ACE2, which is present in low levels, Neuropilin-1 is very abundant in the cells of the nasal cavity. This is a strategically important localization possibly contributing to the efficient infectivity of this new coronavirus, which has caused a major pandemic, spreading rapidly around the world”, Balistreri explains.

    SARS-CoV-2 infects also the upper respiratory system including the nasal mucosa and consequently spreads rapidly. “This virus is able to leave our body even when we simply breath or talk”, Balistreri adds. “The starting point of our study was the question why SARS-CoV, a coronavirus that led to a much smaller outbreak in 2003, and SARS-CoV-2, spread in such a different way even if they use the same main receptor ACE2”, explains Ravi Ojha, a young researcher in the Balistreri’s team, and one of the main contributors of the study.


    A mysterious extra key on the virus surface

    To understand how these differences can be explained, in collaboration with the team of Professor Olli Vapalahti, University of Helsinki, the researchers took a look at the viral surface proteins, the spikes, that, like hooks, anchor the virus to the cells. Balistreri reveals that “when the sequence of the SARS-CoV-2 genome became available, at the end of January, something surprised us. Compared to its older relative, the new coronavirus had acquired an ‘extra piece’ on its surface proteins, which is also found in the spikes of many devastating human viruses, including Ebola, HIV, and highly pathogenic strains of avian influenza, among others. We thought this could lead us to the answer. But how?”

    The turning point of the research was when Ari Helenius, Professor emeritus at the ETH Institute in Zurich, Switzerland, and a former mentor of Balistreri, discussed the matter with two colleagues, Estonian cancer biologists Professor Tambet Teesalu ,University of Tartu, Estonia and Professor Erkki Ruoslahti, University of California, the USA. Professor Teesalu knew that the same sequence acquired by the new coronavirus is also present in certain cellular proteins and hormones that use Neuropilin receptors. Already in 2009, Dr Teesalu and co-workers had suggested that “perhaps, similar to our hormones, viruses that have this key can use neuropilin receptors to gain access into human tissues”.

    Together, the team of scientists looked at whether neuropilins were important for infection by SARS-CoV-2. The experiments performed by Simons, Teesalu and Balistreri teams, together with colleagues from the University of Queensland, Australia, and other research institutions now¨´support this hypothesis. Interestingly, an independent team of scientists at the University of Bristol , UK, has obtained similar results and confirmed that the virus spike binds directly to neuropilin-1 (Ref. DOI: 10.1126/science.abd3072).


    New antiviral strategy in making

    By specifically blocking neuropilin-1 with antibodies, the researchers were able to significantly reduce infection in laboratory cell cultures. “If you think of ACE2 as a door lock to enter the cell, then neuropilin-1 could be a factor that directs the virus to the door. ACE2 is expressed at very low levels in most cells. Thus, it is not easy for the virus to find doors to enter. Other factors such as neuropilin-1 might help the virus finding its door”, says Balistreri.

    Since disorders in smelling are among the symptoms of COVID-19 and neuropilin-1 are known to be localized in the cell layer of the nasal cavity, the scientists examined tissue samples from deceased COVID-19 patients. “We wanted to find out whether cells equipped with neuropilin-1 are really infected by SARS-CoV-2, and found that this was the case, says Mika Simons, Professor of molecular neurobiology at the Technical University of Munich and co-leader of the study.

    Additional studies in mice suggested that neuropilin-1 enables transport from the nasal mucosa to the central nervous system. The animals were administered tiny, virus-sized particles via the nose. These nanoparticles were chemically engineered to link to neuropilin-1. It turned out that after few hours the nanoparticles reached neurons and capillary vessels of the brain, whereas control particles without affinity for neuropilin-1 did not. “We could determine that neuropilin-1, at least under the conditions of our experiments, promotes transport into the brain, but we cannot make any conclusion whether this is also true for SARS-CoV-2. It is very likely that this pathway is suppressed by the immune system in most patients”, Simons says.

    Balistreri cautiously concludes “it is currently too early to speculate whether blocking directly neuropilin could be a viable therapeutic approach, as this could lead to side effects. This will have to be looked at in future studies. Currently our laboratory is testing the effect of new molecules that we have specifically designed to interrupt the connection between the virus and neuropilin. Preliminary results are very promising and we hope to obtain validations in vivo in the near future.”


    Original publication

    Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity, Ludovico Cantuti-Castelvetri et al., Science (2020), DOI: 10.1126/science.abd2985


    Source: University of Helsinki
    = DEATH BEFORE DISHONOR =

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    Face masks required.

    Putin Orders New National Mask Mandate as Russia Sees Second COVID-19 Spike

    Vladimir Putin on Tuesday made his most direct intervention yet to stave off a second wave of novel coronavirus infections by reintroducing a national mask mandate in Russia, The New York Times reports. Masks will reportedly be mandatory in public places like public transport, parking garages, and anywhere where more than 50 people can gather. Since the end of Russia’s first nationwide lockdown, Putin has delegated pandemic measures to regional leaders, so the new mandate marks a change in his government’s thinking. It came as Russia recorded more than 16,000 new cases five days in a row.

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    Quote Originally posted by Dreamtimer View Post
    Face masks required.

    Putin Orders New National Mask Mandate as Russia Sees Second COVID-19 Spike

    Vladimir Putin on Tuesday made his most direct intervention yet to stave off a second wave of novel coronavirus infections by reintroducing a national mask mandate in Russia, The New York Times reports. Masks will reportedly be mandatory in public places like public transport, parking garages, and anywhere where more than 50 people can gather. Since the end of Russia’s first nationwide lockdown, Putin has delegated pandemic measures to regional leaders, so the new mandate marks a change in his government’s thinking. It came as Russia recorded more than 16,000 new cases five days in a row.
    Oh yeah, we have to wear them here too now. Well, we already had to at shops and all that, but now you have to have a mask with/on you at all time. And there are places where you cannot even go anymore without wearing one ─ e.g. the sea dike.
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    Wow.

    A couple months ago I went down into Baltimore and forgot my mask in the car because I wasn't going inside anywhere. It wasn't until I'd walked a few blocks and had a couple people looking at me longer than normal that I realized why.

    So I took my pictures and skedaddled back to my car. No-one actually said anything or gave me grief.

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    Kansas is a nice little petri dish. You can see how counties which enforced mask rules flattened their covid curve.

    And counties which did not enforce masks are now having exponential infection rates.

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    I really doubt the people living in the infectious counties are happy to be a part of such an experiment.

    Apparently the freedom to die and the freedom to be debilitated by disease is...a right?

    Folks have turned freedom and rights back-asswords and catterwomp.

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    Manhattan is the location of Kansas State University and Riley County is the home of the Fort Riley military base.
    “El revolucionario: te meteré la bota en el culo"

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    The situation has been quite bad in Europe and getting worse in the US too. Here in Finland there hasn't been any real lockdowns lately as we have handled the situation quite well, Sweden has a mess in their hands again.

    A room, a bar and a classroom: how the coronavirus is spread through the air

    Europe and US facing new round of shutdowns amid virus surge

    Coronavirus deaths are rising again in the US, as feared

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    Quote Originally posted by Wind View Post
    The situation has been quite bad in Europe and getting worse in the US too. Here in Finland there hasn't been any real lockdowns lately as we have handled the situation quite well, Sweden has a mess in their hands again.

    A room, a bar and a classroom: how the coronavirus is spread through the air

    Europe and US facing new round of shutdowns amid virus surge

    Coronavirus deaths are rising again in the US, as feared
    Belgium has now surpassed 11'000 fatalities due to the coronavirus. We're currently in a state of semi-lockdown. The Flanders is still fairly lax on account of its measures compared to Brussels and the Walloon region ─ they have a stricter curfew than we do. And it's not looking good. We may be headed for a full lockdown again. In fact, we are headed that way due to the alarming numbers, and it's only a matter of time before we hit a concrete wall. The health sector is already getting saturated.

    But it's not just the government that has to fight this. People themselves are lax and careless/irresponsible too.

    To give you an example, when the virus first hit over here, the supermarket personnel was disinfecting the karts in the parking lot. Then a few weeks later, they put a hand sanitizer and a disinfecting spray for the handlebar of the karts at the entrance, along with tissue for wiping the handlebar after spraying it. So then you had to do it yourself. And now, the hand sanitizer is gone from the entrance, and while the spray flask for disinfecting the handlebar is still there, they don't even bother properly mounting the tissue roll into the enclosure anymore ─ for several weeks already ─ so you can't even grab it and tear it off anymore. But hey, you do still have to wear a mask!
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    I wonder how much better the situation would be globally if it wasn't for people's stupidity, indifference and selfishness.

    I guess we'll never know.

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    I had a dream last night and I think it is a telling one:

    I was in a workplace and the company had implemented glass partitions between cubicles and had supplied everyone with masks. A sexy older lady supplying the masks came up very close to me and pulled out two or three masks from her bra and asked me if I had masks and handed them to me. I said, "yeah, I need them" and thanked her. And then I said, "Ich bin ein Berliner" which makes no sense but the co-workers around me just looked at me funny and I repeated to them, "Ich bin ein Berliner" and again they just looked at me and said, "What?". And I said in kidding fashion, "Don't you know what that means?"
    “El revolucionario: te meteré la bota en el culo"

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    medRxiv


    A variant of SARS-CoV-2 emerged in early summer 2020, presumably in Spain, and has since spread to multiple European countries. The variant was first observed in Spain in June and has been at frequencies above 40% since July. Outside of Spain, the frequency of this variant has increased from very low values prior to 15th July to 40-70% in Switzerland, Ireland, and the United Kingdom in September. It is also prevalent in Norway, Latvia, the Netherlands, and France. Little can be said about other European countries because few recent sequences are available. Sequences in this cluster (20A.EU1) differ from ancestral sequences at 6 or more positions, including the mutation A222V in the spike protein and A220V in the nucleoprotein. We show that this variant was exported from Spain to other European countries multiple times and that much of the diversity of this cluster in Spain is observed across Europe. It is currently unclear whether this variant is spreading because of a transmission advantage of the virus or whether high incidence in Spain followed by dissemination through tourists is sufficient to explain the rapid rise in multiple countries.

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    Well, that's it... Belgium is now officially in full lockdown again.
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    wow ... at least they did it. I understand the stressors, trust me, but suicide? I'm not convinced that's the better option.
    “El revolucionario: te meteré la bota en el culo"

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    What part of belgium are you in, Aragorn ... I forgot. I was in Wal-Mart today and literally everyone in the store was wearing a mask except some caucasasian 60'ish lady. When I walked by her she had a smirk on her face and I was thinking, "Suicidal". Then about 15 minutes I walked into a convenience store without my mask on and got stopped by the clerk. I had just stepped out of my car after a short conversation with a consulting firm and was completely focused on that. I had interviewed with the company they use for screening interviews and was told I was given a superior rating (at least in the area of my strength). My day has been kind of weird because I had two interviews and after the 1st one I could tell I was having a 'thinking on my feet' down day. Needless to say the 2nd one went better but still far from flawless. On to the next step I suppose. I've been fighting an infection since sunday and I hope it was a sign of the turning point past it as I have been feeling a little better each day.
    “El revolucionario: te meteré la bota en el culo"

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    I'm going to have to fly again, likely next month. Not really excited about that. But it's family matters.

    Our buffoon of a leader called this a hoax, made up by the Democrats, while he knew the whole time it was dangerous. Now he's just spewing things with no foundation whatsoever. Lord help us all.

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