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MeSH Disease

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Seroprevalence

antibody (1)

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    Functional pangenome analysis provides insights into the origin, function and pathways to therapy of SARS-CoV-2 coronavirus MESHD

    Authors: Intikhab Alam; Allan K Kamau; Maxat Kulmanov; Stefan T Arold; Arnab T Pain; Takashi Gojobori; Carlos M. Duarte

    doi:10.1101/2020.02.17.952895 Date: 2020-02-21 Source: bioRxiv

    The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins from SARS-CoV-1 and SARS-CoV-2 MESHD are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1-specific neutralizing antibodies SERO to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema HP edema MESHD in lungs causing the acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD)4-6, the leading cause of death MESHD in SARS-CoV-1 and SARS-CoV-2 infection7 MESHD SARS-CoV-2 infection MESHD7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.

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MeSH Disease
Transmission
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