{"id":1528,"date":"2020-12-15T12:19:29","date_gmt":"2020-12-15T12:19:29","guid":{"rendered":"http:\/\/horizon.peachpuff-wolverine-566518.hostingersite.com\/?p=1528"},"modified":"2020-12-15T12:19:29","modified_gmt":"2020-12-15T12:19:29","slug":"qa-how-covid-19-hijacks-human-cells","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/horizon\/1528\/qa-how-covid-19-hijacks-human-cells\/","title":{"rendered":"Q&A: How Covid-19 hijacks human cells"},"content":{"rendered":"
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The virus that causes<\/span><\/strong>\u00a0Covid-19\u00a0<\/span><\/strong>hijacks human cells by exploiting a\u00a0<\/span><\/strong>\u2018<\/span><\/strong>doorway<\/span><\/strong>\u2019<\/span><\/strong>\u00a0that is\u00a0<\/span><\/strong>potentially\u00a0<\/span><\/strong>also used by<\/span><\/strong>\u00a0<\/span><\/strong>other deadly viruses such as HIV,\u00a0<\/span><\/strong>d<\/span><\/strong>engue<\/span><\/strong>\u00a0and Ebola, according to recent research that may help to explain why the coronavirus is so highly infectious to a wide range of organs in the body.<\/span><\/strong>\u00a0<\/span><\/p>\n

Dr\u00a0<\/span><\/strong>Yohei<\/span><\/strong>\u00a0Yamauchi<\/span><\/strong>, a viral cell biologist at the University of Bristol<\/span><\/strong>, UK,\u00a0<\/span><\/strong>who\u00a0<\/span><\/strong>led the research, believes that the finding could not only lead to new drugs against Covid-19, but other anti-viral treatments that could be used to save patients<\/span><\/strong>\u2019<\/span><\/strong>\u00a0lives in future pandemics.<\/span><\/strong>\u00a0<\/span><\/p>\n<\/div>\n<\/div>\n<\/div>\n

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Why is the molecular biology of viruses important?<\/span><\/strong><\/p>\n

I\u2019ve always been interested in how cells are hijacked by viruses. When you look at a virus through a microscope, you can only see so much because they are really small compared to a cell. It is a bit like looking at a building from a satellite \u2013 you can\u2019t see the people inside or how they open the doors to get in. I\u2019m trying to understand how a virus opens the door to get inside the cell and take it over at a molecular level\u00a0<\/span>\u2013<\/span>\u00a0what cellular proteins and processes are involved.<\/span><\/p>\n

How did you end up working on Covid-19?<\/span><\/strong><\/p>\n

For several years I have been studying flu and a few other viruses like\u00a0<\/span>Z<\/span>ika and\u00a0<\/span>HIV-1<\/span>\u00a0(the most common HIV virus)<\/span>. We have been finding that many viruses use the same doors to get into a cell, but open them in their own individual ways. When the genetic sequence of Sars-CoV-2 (the virus that causes Covid-19) was published in February, we immediately recognised part of the sequence that codes for the spike protein.<\/span><\/p>\n

What is the spike protein?<\/span><\/strong><\/p>\n

The Sars-CoV-2 virus has all these spikes sticking up from the virus particle that make it look like a crown \u2013 that\u00a0<\/span>is\u00a0<\/span>why<\/span>it is called a coronavirus (corona is\u00a0<\/span>Latin<\/span>\u00a0for crown). These spikes are proteins that are like a hook on the outside of the virus particle, which allow it to\u00a0<\/span>recognise and bind to human proteins<\/span><\/a>\u00a0on the surface of cells. Without the spike protein, the virus would have no way of sticking to the surface of cells and infecting them.<\/span><\/p>\n

The spike protein is also the ideal target for vaccines \u2013 both the\u00a0<\/span>Moderna<\/span>\u00a0and Pfizer<\/span>\/<\/span>BioNTech<\/span>\u00a0vaccines target the spike protein \u2013 so understanding\u00a0<\/span>it<\/span>\u00a0help<\/span>s<\/span>\u00a0to improve them.<\/span><\/p>\n

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Dr Yamauchi says that drugs that interrupt neuropilin 1 binding could be used against of a wide variety of viruses, including those that may emerge in future pandemics. Image credit – Yohei Yamauchi<\/figcaption><\/figure>\n<\/div>\n

What caught your eye about the Covid-19 spike protein?<\/span><\/strong><\/p>\n

The spike protein really differentiates this coronavirus from previous\u00a0<\/span>ones.<\/span>W<\/span>e know about the ones that cause S<\/span>ARS<\/span>\u00a0or M<\/span>ERS<\/span>. It\u2019s got these specific, unique sequences at the molecular level that allow it to bind to proteins on the cell surface. At some point this\u00a0<\/span>(novel) corona<\/span>virus obtained a sequence in its spike protein that allows it to be cleaved in two by an enzyme found in its host (humans) called\u00a0<\/span>furin<\/span>. We had seen this\u00a0<\/span>furin<\/span>\u00a0cleavage in other viruses such as in the H5N1 highly pathogenic avian flu virus, where it appears\u00a0<\/span>in\u00a0<\/span>the flu equivalent of the spike protein. Other pathogenic viruses also have\u00a0<\/span>furin<\/span>\u00a0cleavage sites on the proteins that bind to cells \u2013 HIV, Ebola and\u00a0<\/span>Crimean-Congo\u00a0<\/span>haemorrhagic<\/span>\u00a0fever virus<\/span>all have them.<\/span><\/p>\n

Why is this important?<\/span><\/strong><\/p>\n

The scientific community<\/span>\u00a0already knew that\u00a0<\/span>Sars-<\/span>CoV<\/span>–<\/span>2 had at some point obtained the ability to bind with a\u00a0<\/span>greater affinity<\/span><\/a>\u00a0to a receptor protein (a type of protein on the surface of a cell)\u00a0<\/span>called ACE2<\/span><\/a>\u00a0compared to the S<\/span>ARS<\/span>\u00a0coronavirus. But when the\u00a0<\/span>furin<\/span>\u00a0cleaves the spike protein, it exposes a new sequence which allows it to bind to another host cell protein and hijack its function. We\u00a0<\/span>identified that protein as\u00a0<\/span>neuropilin<\/span>\u00a01<\/span><\/a>\u00a0and<\/span>\u00a0it could be this that makes\u00a0<\/span>Sars-<\/span>CoV<\/span>–<\/span>2 so highly infectious<\/span>\u00a0in many organs.<\/span><\/p>\n

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\u2018<\/span><\/span>I\u2019m trying to understand how a virus opens the door to get inside the cell and take it over at a molecular level\u00a0<\/span><\/span>\u2013<\/span><\/span>\u00a0what cellular proteins and processes are involved.<\/span><\/span>\u2019<\/span><\/span><\/p>\n

-Dr Yohei Yamauchi, University of Bristol, UK<\/span><\/p>\n<\/blockquote>\n

What does\u00a0<\/span><\/strong>neuropilin<\/span><\/strong>\u00a01 normally do<\/span><\/strong>\u00a0in the body<\/span><\/strong>?<\/span><\/strong><\/p>\n

Neuropilin<\/span>\u00a01 is a receptor protein found on the surface of\u00a0<\/span>many\u00a0<\/span>cells that triggers the\u00a0<\/span>transportation\u00a0<\/span>of the molecules that bind to it<\/span>\u00a0inside the cell<\/span>. It also\u00a0<\/span>allows<\/span>\u00a0molecules\u00a0<\/span>to<\/span>\u00a0be passed from cell to cell. In 3D tissue, that means something binding\u00a0<\/span>to<\/span>neuropilin<\/span>\u00a01 on the top layer of cells could easily reach the middle layers of cells.\u202f<\/span><\/p>\n

Some people in cancer biology are very interested in it for this reason. If you can trigger\u00a0<\/span>neuropilin<\/span>\u00a01, you can increase the uptake of small drug molecules into otherwise solid tumours.\u202f<\/span><\/p>\n

How does this help the virus?\u00a0<\/strong><\/p>\n

This is still a hypothesis, but we think viruses able to trigger\u00a0<\/span>neuropilin<\/span>\u00a01 might be able to dig deeper into tissues without first having to replicate\u00a0<\/span>themselves\u00a0<\/span>in the upper layer of cells. That would be an amazing bypassing mechanism for a virus.\u202f<\/span><\/p>\n

Would that make it harder for the immune system to spot them too?<\/span><\/strong><\/p>\n

Exactly. And it would eventually mean the virus spreads quicker. It would help to give it this broad tropism\u00a0<\/span>(ability to infect\u00a0<\/span>many different<\/span>\u00a0organs and tissues<\/span>)<\/span>we are seeing<\/span>\u00a0in\u00a0<\/span>Covid-19 compared to the coronavirus that caused S<\/span>ARS<\/span>, which doesn\u2019t have that\u00a0<\/span>furin<\/span>\u00a0cleavage site. The current virus is able to cause neurological symptoms like loss of smell, and taste, it is causing\u00a0<\/span>myocarditis<\/span><\/a>\u00a0(inflammation of the heart) in some patients, as well as going to the lungs.<\/span><\/p>\n

We think the CoV-2 virus might be using\u00a0<\/span>neuropilin<\/span>\u00a01 to facilitate traffick<\/span>ing<\/span>\u00a0into other\u00a0<\/span>types of\u00a0<\/span>cells by binding to cells on the surface of tissue<\/span>s<\/span>\u00a0that have\u00a0<\/span>neuropilin<\/span>\u00a01.<\/span><\/p>\n

Can we use\u00a0<\/span><\/strong>neuropilin<\/span><\/strong>\u00a01 to find new treatments for Covid-19?<\/span><\/strong><\/p>\n

We are doing a follow up study on this, but we found that by interrupting the interaction between the viral spike protein and\u00a0<\/span>neuropilin<\/span>\u00a01 we can\u00a0<\/span>decrease infectivity in human cell cultures<\/span><\/a>. Due to the intense study in cancer biology on\u00a0<\/span>neuropilin<\/span>\u00a01, there are already\u00a0<\/span>neuropilin<\/span>\u00a01-neutralising antibodies that have been in phase 2a clinical trials in the US against certain types of cancer. There is also a small molecule antagonist that competes with other molecules at the\u00a0<\/span>neuropilin<\/span>\u00a01<\/span>\u00a0binding site. Those are already out there, so by fine tuning them and improving their\u00a0<\/span>af<\/span>finity<\/span>\u00a0(ability to bind to\u00a0<\/span>neuropilin<\/span>)<\/span>, we could produce some sort of drug that interrupts the interaction of the virus spike protein with\u00a0<\/span>neuropilin<\/span>\u00a01. It could be effective in reducing the severity of disease in patients.<\/span><\/p>\n

\"\"<\/a>
Researchers have discovered that the coronavirus spike protein can bind to a receptor called neuropilin 1, which gives it another way to enter human cells. Image credit – Ryan Allen<\/figcaption><\/figure>\n<\/div>\n

What are you doing next?<\/span><\/strong>\u00a0<\/span><\/p>\n

We have found that the spike protein can bind to\u00a0<\/span>neuropilin<\/span>\u00a01 in more than one place \u2013 it has at least two binding sites. The virus probably originated binding just at one place. Then it found by gaining this\u00a0<\/span>furin<\/span>\u00a0binding site, it either increased\u00a0<\/span>binding strength\u00a0<\/span>or triggered internalisation. We are now trying to understand its whole interaction. We have some preliminary data that if we can block the spike protein from binding to\u00a0<\/span>neuropilin<\/span>\u00a01 completely, it really impacts infectivity even more.<\/span>\u00a0<\/span><\/p>\n

What might your research lead to longer term?<\/span><\/strong>\u00a0<\/span><\/p>\n

My theory is that\u00a0<\/span>neuropilin<\/span>\u00a01 has been and always will be a favoured receptor for a lot of viruses because of its multi<\/span>–<\/span>functionality in helping internalisation and spread through tissues. Each virus seems to have found a different way to bind to it.<\/span>\u00a0<\/span><\/p>\n

It seems almost unavoidable that a future pandemic will also be caused by a virus that also binds to\u00a0<\/span>neuropilin<\/span>\u00a01. If we had a drug in advance that interrupts this interaction, we could use it at a very early stage of a pandemic and hopefully save patients\u2019 lives.\u202f<\/span>\u00a0<\/span><\/p>\n

That is really the aim of the wider\u00a0<\/span>CHUbVi<\/span>\u00a0project<\/span><\/a>\u00a0that I am part of \u2013 we want to target the mechanisms viruses use to get into cells to make broad-spectrum antiviral drugs that can be used against a number of viruses.<\/span>\u00a0<\/span><\/p>\n

The research in this article was funded by the EU’s European\u00a0<\/span><\/em>Research Council<\/span><\/em>.\u00a0<\/span><\/em>If you liked this article, please consider sharing it on social media.<\/span><\/em><\/p>\n

This article was originally published on Horizon magazine<\/a>.<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

The virus that causes\u00a0Covid-19\u00a0hijacks human cells by exploiting a\u00a0\u2018doorway\u2019\u00a0that is\u00a0potentially\u00a0also used by\u00a0other deadly viruses such as HIV,\u00a0dengue\u00a0and Ebola, according to recent research that may help to explain why the coronavirus is so highly infectious to a wide range of organs in the body.\u00a0 Dr\u00a0Yohei\u00a0Yamauchi, a viral cell biologist at the University of Bristol, UK,\u00a0who\u00a0led the … Read more<\/a><\/p>\n","protected":false},"author":298,"featured_media":1531,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"generate_page_header":"","jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[12],"tags":[359,360,169,37],"class_list":["post-1528","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health","tag-coronavirus","tag-covid-19","tag-frontier-research","tag-health"],"yoast_head":"\nQ&A: How Covid-19 hijacks human cells - Horizon Magazine Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/horizon\/1528\/qa-how-covid-19-hijacks-human-cells\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Q&A: How Covid-19 hijacks human cells\" \/>\n<meta property=\"og:description\" content=\"The virus that causes\u00a0Covid-19\u00a0hijacks human cells by exploiting a\u00a0\u2018doorway\u2019\u00a0that is\u00a0potentially\u00a0also used by\u00a0other deadly viruses such as HIV,\u00a0dengue\u00a0and Ebola, according to recent research that may help to explain why the coronavirus is so highly infectious to a wide range of organs in the body.\u00a0 Dr\u00a0Yohei\u00a0Yamauchi, a viral cell biologist at the University of Bristol, UK,\u00a0who\u00a0led the ... 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A second one is hot on its heels. The two \u2013 one made by Pfizer\/BioNTech and the other by Moderna \u2013 mark the first time this\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/scienceblog.com\/horizon\/category\/health\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/12\/ChildVaccine.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/12\/ChildVaccine.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/12\/ChildVaccine.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/12\/ChildVaccine.jpg?resize=700%2C400&ssl=1 2x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/12\/ChildVaccine.jpg?resize=1050%2C600&ssl=1 3x"},"classes":[]}],"_links":{"self":[{"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/posts\/1528","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/users\/298"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/comments?post=1528"}],"version-history":[{"count":0,"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/posts\/1528\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/media\/1531"}],"wp:attachment":[{"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/media?parent=1528"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/categories?post=1528"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceblog.com\/horizon\/wp-json\/wp\/v2\/tags?post=1528"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}