Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence

There are no seroprevalence terms in the subcorpus

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    Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2

    Authors: Ziwei Yang; Xiaolin Zhang; Fan Wang; Peihui Wang; Xiaojuan Li; Ersheng Kuang

    doi:10.1101/2020.08.12.247767 Date: 2020-08-12 Source: bioRxiv

    Melanoma MESHD Melanoma HP differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses MESHD. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKK, subsequently leading to IRF3 and NF-{kappa}B phosphorylation. Great numbers of symptomatic and severe infections HP infections MESHD of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses MESHD. It downregulates the expression of type I IFNs, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 mediates innate immune evasion during SARS-CoV-2 infection MESHD and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases MESHD.

    Antiviral activity of Glucosylceramide synthase inhibitors against SARS-CoV-2 and other RNA virus infections MESHD

    Authors: Einat B. Vitner; Roy Avraham; Hagit Achdout; Hadas Tamir; Avi Agami; Lilach Cherry; Yfat Yahalom-Ronen; Boaz Politi; Noam Erez; Sharon Melamed; Nir Paran; Tomer Israely

    doi:10.1101/2020.05.18.103283 Date: 2020-05-19 Source: bioRxiv

    The need for antiviral drugs is real and relevant. Broad spectrum antiviral drugs have a particular advantage when dealing with rapid disease MESHD outbreaks, such as the current COVID-19 pandemic. Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga(R), (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission TRANS route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 pandemic, this may be particularly relevant to SARS-CoV-2 infection MESHD. One Sentence SummaryAn analogue of Cerdelga(R), an FDA-approved drug, is effective against a broad range of RNA-viruses including the newly emerging SARS-CoV-2.

    Enisamium is a small molecule inhibitor of the influenza A virus and SARS-CoV-2 RNA polymerases

    Authors: Alexander Walker; Haitian Fan; Jeremy R Keown; Victor Margitich; Jonathan M Grimes; Ervin Fodor; Aartjan JW te Velthuis

    doi:10.1101/2020.04.21.053017 Date: 2020-04-21 Source: bioRxiv

    Influenza A virus and coronavirus strains cause a mild to severe respiratory disease MESHD that can result in death MESHD. Although vaccines exist against circulating influenza A viruses, such vaccines are ineffective against emerging pandemic influenza A viruses. Currently, no vaccine exists against coronavirus infections MESHD, including pandemic SARS-CoV-2, the causative agent of the Coronavirus Disease MESHD 2019 (COVID-19). To combat these RNA virus infections MESHD, alternative antiviral strategies are needed. A key drug target is the viral RNA polymerase, which is responsible for viral RNA synthesis. In January 2020, the World Health Organisation identified enisamium as a candidate therapeutic against SARS-CoV-2. Enisamium is an isonicotinic acid derivative that is an inhibitor of multiple influenza B and A virus strains in cell culture and clinically approved in 11 countries. Here we show using in vitro assays that enisamium and its putative metabolite, VR17-04, inhibit the activity of the influenza virus and the SARS-CoV-2 RNA polymerase. VR17-04 displays similar efficacy against the SARS-CoV-2 RNA polymerase as the nucleotide analogue remdesivir triphosphate. These results suggest that enisamium is a broad-spectrum small molecule inhibitor of RNA virus RNA synthesis, and implicate it as a possible therapeutic option for treating SARS-CoV-2 infection MESHD. Unlike remdesivir, enisamium does not require intravenous administration which may be advantageous for the development of COVID-19 treatments outside a hospital setting. ImportanceInfluenza A virus and SARS-CoV-2 are respiratory viruses capable of causing pandemics, and the latter is responsible for the Coronavirus Disease MESHD 2019 (COVID-19) pandemic. Both viruses encode RNA polymerases which transcribe their RNA genomes and are important targets for antiviral drugs including remdesivir. Here, we show that the antiviral drug enisamium inhibits the RNA polymerases of both influenza A virus and SARS-CoV-2. Furthermore, we show that a putative metabolite of enisamium is a more potent inhibitor, inhibiting the SARS-CoV-2 RNA polymerase with similar efficiency to remdesivir. Our data offer insight into the mechanism of action for enisamium, and implicate it as a broad-spectrum antiviral which could be used in the treatment of SARS-CoV-2 infection MESHD.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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