How SARS-CoV-2 binds to human cells

Fora ASTRO-FORUM NYT FRA VIDENSKABEN How SARS-CoV-2 binds to human cells

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  • #325238

    Bjarne
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    • Super Nova

    https://science.sciencemag.org/content/367/6485/1444
    Science 27 Mar 2020:
    Vol. 367, Issue 6485, pp. 1444-1448
    DOI: 10.1126/science.abb2762

    Abstract

    Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.

    Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans. The resulting outbreak of coronavirus disease 2019 (COVID-19) has emerged as a severe epidemic, claiming more than 2000 lives worldwide between December 2019 and February 2020. The genome of SARS-CoV-2 shares about 80% identity with that of SARS-CoV and is about 96% identical to the bat coronavirus BatCoV RaTG13.

    In the case of SARS-CoV, the spike glycoprotein (S protein) on the virion surface mediates receptor recognition and membrane fusion. During viral infection, the trimeric S protein is cleaved into S1 and S2 subunits and S1 subunits are released in the transition to the postfusion conformation. S1 contains the receptor binding domain (RBD), which directly binds to the peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2), whereas S2 is responsible for membrane fusion. When S1 binds to the host receptor ACE2, another cleavage site on S2 is exposed and is cleaved by host proteases, a process that is critical for viral infection. The S protein of SARS-CoV-2 may also exploit ACE2 for host infection. A recent publication reported the structure of the S protein of SARS-CoV-2 and showed that the ectodomain of the SARS-CoV-2 S protein binds to the PD of ACE2 with a dissociation constant (Kd) of ~15 nM.

    Jeg er ikke molekylærbiolog, men ovenstående forkortelser kan måske hjælpe med til at forstå denne ledsagende forklaring:

    How SARS-CoV-2 binds to human cells

    Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan et al. present the structure of human ACE2 in complex with a membrane protein that it chaperones, B0AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction.

    Artiklen viser under alle omstændigheder, at elektronmikroskopet og kvantemekanik er helt afgørende videnskabelige teorier for udviklingen af et middel mod sygdommen COVID-19. Aristoteles’ formålsbestemte årsager virker ikke.

    #325242

    Bjarne
    Moderator
    • Super Nova

    https://www.weekendavisen.dk/2020-13/ideer/haabets-budbringer

    Håbets budbringer

    Med et lille stykke råt arvemateriale kan man få kroppen til at vaccinere sig selv. I årtier er der blevet kigget skævt til metoden, men nu har den ført til de første kliniske forsøg med en COVID-19-vaccine. Lykkes det, kan det betyde en ende på pandemierne.

    Gunver Lystbæk Vestergård er også forfatter af bogen:
    FJERNE KLODER
    Historienom opdagelsen af exoplaneter og jagten på verdener som vores.

    #325243

    Bjarne
    Moderator
    • Super Nova

    Der findes et våben mod corona vira og multiresistente bakterier: Far-UVC lys. Se denne TED talk:
    https://www.ted.com/talks/david_brenner_a_new_weapon_in_the_fight_against_superbugs
    Jeg ved ikke, hvorfor der ikke er mere fokus på denne simple løsning.

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