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Science

Researchers Discover Second 'Key' Used By Coronavirus To Enter Human Cells (helsinki.fi) 41

Kiuas writes: Researchers from the Technical University of Munich and the University of Helsinki have discovered a second receptor (called neuropilin-1) which is used by the SARS-CoV-2 virus to enter into human cells via the nasal cavity.

The discovery is important as it helps explain the rapid spread of the virus, and also helps define a potential target for antirviral intervention... The study itself was published in the Science magazine on the 20th of October.

More details announced by the University of Helsinki: "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 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...

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...

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."

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Researchers Discover Second 'Key' Used By Coronavirus To Enter Human Cells

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  • The summary leaves out some important and fascinating context here.

    The researchers were actually studying chronic pain. Neuropilin-1 seems to be associated with pain, meaning that in the initial stages of the infection, you may actually feel BETTER, especially if you're a chronic pain sufferer. Some people have contacted one of the researchers saying that not only did their pain disappear when they had the infection, but also after the infection had cleared.

    Here's [www.cbc.ca] a link to a short article and the podcast segment on CBC's science podcast.

    So if you wake up feeling really good one morning, look out, you might be sick. Just what we all want to hear.

  • Clothespins (Score:2, Interesting)

    by Anonymous Coward
    This discovery forces me to wonder whether using a clothespin to "cinch" shut the nostrils, rather than wearing a mask, could effectively block transmission of the virus through the nasal cavity. This new approach could save hundreds of thousands of lives and revolutionize the approach that we take to keep America open for business through the winter. This could be the bridge to a vaccine we've all been waiting for.
    • Re:Clothespins (Score:5, Interesting)

      by jenningsthecat ( 1525947 ) on Saturday October 24, 2020 @06:13PM (#60644444)

      This discovery forces me to wonder whether using a clothespin to "cinch" shut the nostrils, rather than wearing a mask, could effectively block transmission of the virus through the nasal cavity.

      I think you're joking, but I in all seriousness considered something similar. We know that at some point the viral load passes some (variable, individual) threshold and causes infection, and that prior to reaching that threshold the body's front-line defenses are enough to prevent infection. If we blocked our nasal cavities and breathed through our mouths, might that not effectively raise the threshold at which we become infected?

  • Blocking neuropilin (Score:4, Interesting)

    by backslashdot ( 95548 ) on Saturday October 24, 2020 @04:51PM (#60644254)

    When it comes to treatment it's probably not a good idea to block neuropilin-1 -- for various reasons (unless you are luck and can have a way do it really carefully so that its normal function is unaffected). It's more likely that the best way for a treatment is to have a molecule that attaches to the portion of the Spike protein that attaches to the neuropilin and pray that the virus can't mutate around that.

    • by BarbaraHudson ( 3785311 ) <barbara.jane.hud ... minus physicist> on Saturday October 24, 2020 @05:55PM (#60644406) Journal
      The best way would be to test for T cell immunity to existing coronaviruses.

      There are 4 human coronaviruses that cause colds, and about 35% of the population has T cells that kill them. Tests show they also react to this coronavirus, so we may be sitting around with a goodly chunk of the population who will, at most, feel a bit out of sorts for a few hours.

      Not nearly as profitable as a vaccine that probably won't be all that effective and would need injections every 6 months, which is far more profitable.

      There's also some indication that the bcg vaccine (used against tuberculosis and as an adjuvant in other vaccines because it provokes a response from the innate immune system (T1 white blood cells and B cells) can give some sort of immunity to covid. The problem is that it's highly dependent on the strain used for the tb vaccine, as well as the medium it was grown in. Also, many people don't maintain lifetime immunity to Tb after a vaccination - but many do.

      • by backslashdot ( 95548 ) on Saturday October 24, 2020 @06:45PM (#60644494)

        It's not as simple as testing for existing immunity for the following reasons:

        90% of the population is seropositive to at least one of those Coronaviruses. Reference: https://www.nature.com/article... [nature.com]. However not all of pre-existing immunity recognizes the covid-19's Spike protein efficiently. Reference: https://www.cell.com/cell/full... [cell.com]

        Also, pre-existing immunity to the SAME coronavirus seems to be ineffective within a year. Reference: https://www.ncbi.nlm.nih.gov/p... [nih.gov].

        If we can't sustain effective immunity to the same strain of a coronavirus, how can we guarantee effective cross-immunity? You may end up increasing the number of super spreaders handing it to vulnerable people before a vaccine is available.

        The BCG vaccine isn't very good against this coronavirus, most early speculation was based on false correlation. Reference: https://academic.oup.com/cid/a... [oup.com] Using it against Covid will prevent it from being used where TB is endemic.

        • If we can't sustain effective immunity to the same strain of a coronavirus, how can we guarantee effective cross-immunity? You may end up increasing the number of super spreaders handing it to vulnerable people before a vaccine is available. Could you please explain this part a little more? What would be a possibly sequence of events that would lead to more superspreaders? (Genuine question... Iâ(TM)m interested.)
        • Could you please explain this part a little more?

          If we can't sustain effective immunity to the same strain of a coronavirus, how can we guarantee effective cross-immunity? You may end up increasing the number of super spreaders handing it to vulnerable people before a vaccine is available.

          What would be a possibly sequence of events that would lead to more superspreaders? (Genuine question... I'm interested.)

          • Two things may cause it.

            1. When the body encounters what it thinks is a previously seen pathogen, it gives up on developing a new response and leans on the "memory cells" which produce the antibodies used to win against the previously encountered pathogen. Reference: https://en.wikipedia.org/wiki/... [wikipedia.org]. All of those old antibodies may not bind to the new pathogen because many of the targets (called epitopes) are slightly different -- and many of the ones that do bind to a target may not even neutralize it.

    • Enter University of Queensland Gene Clamp tech. Everyone else has chosen the traditional approach. Maybe the university has missed pain management may be more profitable than a vaccine.
  • by 93 Escort Wagon ( 326346 ) on Saturday October 24, 2020 @05:01PM (#60644280)

    Science Good.

  • I wish people who should know better would stop using such active language when describing what is an evolutionary process.

    "viruses often use multiple factors to maximize their infectious potential"

    This makes it sound like the virus has constructed itself to deliberately target humans.

  • A better article (Score:5, Informative)

    by kbahey ( 102895 ) on Saturday October 24, 2020 @06:38PM (#60644482) Homepage

    Here is a better article [medicalxpress.com] on how Neuropilin-1 is involved in SARS-CoV-2 entry into cells, how it was done, and the implications.

    If this pans out, then we can have a prophylactic (preventative) drug, which is neither a vaccine, or a therapeutic (treatment).

    Very much like how certain pills are taken for malaria.

  • . "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.

    How do you "direct' a virus? It's not like a bacteria that has a behavior you can affect - I thought virons were all inert protein capsules that float around without power or direction, that has to bump into the receptor it needs to lock on and get pulled into a cell?

  • This isn't news. It was first announced in a preprint dated June 7: https://www.biorxiv.org/conten... [biorxiv.org]

When your work speaks for itself, don't interrupt. -- Henry J. Kaiser

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