{"id":765,"date":"2020-05-05T10:46:47","date_gmt":"2020-05-05T05:16:47","guid":{"rendered":"http:\/\/www.potentialloops.org\/?p=765"},"modified":"2020-05-05T10:46:49","modified_gmt":"2020-05-05T05:16:49","slug":"activation-of-the-sars-coronavirus-2-revealed","status":"publish","type":"post","link":"https:\/\/www.potentialloops.org\/?p=765","title":{"rendered":"Activation of the SARS coronavirus 2 revealed"},"content":{"rendered":"\n

Infection researchers identify starting points for vaccine development and therapy <\/h4>\n\n\n\n

Date: May 4, 2020 <\/p>\n\n\n\n

Source 1: Deutsches Primatenzentrum (DPZ)\/German Primate Center <\/p>\n\n\n\n

Source 2: www.sciencedaily.com<\/a><\/p>\n\n\n\n

Summary: A viral spike protein mediates entry of SARS-CoV-2 into host cells and harbors an unusual activation sequence. This sequence is cleaved by the cellular enzyme furin and the cleavage is important for the infection of lung cells. These results define new starting points for therapy and vaccine research. In addition, they provide information on how coronaviruses from animals need to change in order to be able to spread in the human population. <\/p>\n\n\n\n

The SARS coronavirus 2 (SARS-CoV-2) infects \nlung cells and is responsible for the COVID-19 pandemic. The viral spike\n protein mediates entry of the virus into host cells and harbors an \nunusual activation sequence. The Infection Biology Unit of the German \nPrimate Center (DPZ) — Leibniz Institute for Primate Research has now \nshown that this sequence is cleaved by the cellular enzyme furin and \nthat the cleavage is important for the infection of lung cells. These \nresults define new starting points for therapy and vaccine research. In \naddition, they provide information on how coronaviruses from animals \nneed to change in order to be able to spread in the human population (Molecular Cell<\/em>).<\/p>\n\n\n\n

The new coronavirus SARS-CoV-2 has been transmitted from animals to \nhumans and is spreading worldwide. It causes the new lung disease \nCOVID-19, which has already killed over 200,000 people. The spike \nprotein on the virus surface serves as a key for the virus to enter host\n cells. It facilitates viral attachment to cells and fuses the viral \nwith a cellular membrane, thereby allowing the virus to deliver its \ngenome into the cell, which is essential for viral replication. For \nthis, activation sequences of the spike protein need to be cleaved by \ncellular enzymes, called proteases. The spike protein of SARS-CoV-2 \ncarries an activation sequence at the so-called S1\/S2 cleavage site, \nwhich is similar to those observed in highly pathogenic avian influenza \nviruses, but which has so far not been found in viruses closely related \nto SARS-CoV-2. The importance of this sequence for the virus was so far \nunknown.<\/p>\n\n\n\n

In their current study, the infection biologists of the German \nPrimate Center led by Markus Hoffmann and Stefan P\u00f6hlmann were able to \nshow that the S1\/S2 activation sequence of the SARS-CoV-2 spike protein \nis cleaved by the cellular protease furin and that this cleavage event \nis essential for the infection of lung cells. It is also important for \nthe fusion of infected cells with non-infected cells, which might allow \nthe virus to spread in the body without leaving the host cell.<\/p>\n\n\n\n

“Our results suggest that inhibition of furin should block the spread\n of SARS-CoV-2 in the lung,” says Stefan P\u00f6hlmann, head of the Infection\n Biology Unit at DPZ. “Furthermore, our present study and previous work \ndemonstrate that the virus uses a two-step activation mechanism: In \ninfected cells, the spike protein has to be cleaved by the protease \nfurin so that newly formed viruses can then use the protease TMPRSS2 for\n further cleavage of the spike protein, which is important for the entry\n into lung cells.”<\/p>\n\n\n\n

Development of live attenuated vaccines<\/strong><\/p>\n\n\n\n

For a live attenuated vaccine to trigger a strong immune response, it\n has to be able to replicate in the body to a limited extent, for \nexample locally at the site of injection. “SARS-CoV-2 variants, in which\n the activation sequence for furin has been removed, could be used as a \nbasis for the development of such live attenuated vaccines, since the \nlack of cleavage of the spike protein should greatly limit the spread of\n the virus in the body. A sufficiently attenuated virus would no longer \nbe able to cause disease, but would still enable the immune system to \nreact to the pathogen and, for example, produce neutralizing \nantibodies,” says Markus Hoffmann, first author of the study.<\/p>\n\n\n\n

Risk assessment<\/strong><\/p>\n\n\n\n

In wildlife, especially bats, a large number of coronaviruses that are closely related to SARS-CoV and SARS-CoV-2 has been discovered over the past 20 years. However, so far an S1\/S2 activation sequence that can be cleaved by furin has only been detected in SARS-CoV-2. “Wildlife sampling and the targeted search for coronaviruses with a focus on the S1\/S2 activation sequence is necessary to identify those viruses that have the potential to infect and efficiently spread in humans. In addition, in the case of potential future coronavirus outbreaks, we should specifically analyze the S1\/S2 cleavage site as it might serve as a marker for human-to-human transmissibility,” says Markus Hoffmann.<\/p>\n\n\n\n

Story Source:<\/strong><\/p>\n\n\n\n

Materials<\/a> provided by Deutsches Primatenzentrum (DPZ)\/German Primate Center<\/strong><\/a>. Note: Content may be edited for style and length.<\/em><\/p>\n\n\n\n

www.sciencedaily.com<\/a><\/p>\n\n\n\n

\n\n\n\n

Journal Reference<\/strong>:<\/p>\n\n\n\n

  1. Markus Hoffmann, Hannah Kleine-Weber, Stefan P\u00f6hlmann. A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells<\/strong>. Molecular Cell<\/em>, 2020; DOI: 10.1016\/j.molcel.2020.04.022<\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    Infection researchers identify starting points for vaccine development and therapy Date: May 4, 2020 Source 1: Deutsches Primatenzentrum (DPZ)\/German Primate Center Source 2: www.sciencedaily.com Summary: A viral spike protein mediates entry of SARS-CoV-2 into host cells and harbors an unusual activation sequence. This sequence is cleaved by the cellular enzyme furin and the cleavage is […]<\/p>\n","protected":false},"author":1,"featured_media":766,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_coblocks_attr":"","_coblocks_dimensions":"","_coblocks_responsive_height":"","_coblocks_accordion_ie_support":"","om_disable_all_campaigns":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_uf_show_specific_survey":0,"_uf_disable_surveys":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[35],"tags":[94,57,58,40,52,68,93,96,54],"class_list":["post-765","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-coronavirus","tag-animal","tag-coronavirus","tag-proteins","tag-research","tag-sars-cov-2","tag-spread","tag-therapy","tag-transmission","tag-vaccine"],"aioseo_notices":[],"yoast_head":"\nActivation of the SARS coronavirus 2 revealed -<\/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:\/\/www.potentialloops.org\/?p=765\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Activation of the SARS coronavirus 2 revealed -\" \/>\n<meta property=\"og:description\" content=\"Infection researchers identify starting points for vaccine development and therapy Date: May 4, 2020 Source 1: Deutsches Primatenzentrum (DPZ)\/German Primate Center Source 2: www.sciencedaily.com Summary: A viral spike protein mediates entry of SARS-CoV-2 into host cells and harbors an unusual activation sequence. 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