Corpus overview


Overview

MeSH Disease

Human Phenotype

Hepatitis (2)


Transmission

There are no transmission terms in the subcorpus


Seroprevalence

There are no seroprevalence terms in the subcorpus

    displaying 1 - 2 records in total 2
    records per page




    Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase

    Authors: Minchen Chien; Thomas K. Anderson; Steffen Jockusch; Chuanjuan Tao; Shiv Kumar; Xiaoxu Li; James J. Russo; Robert Kirchdoerfer; Jingyue Ju

    doi:10.1101/2020.03.18.997585 Date: 2020-03-20 Source: bioRxiv

    SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis HP hepatitis MESHD C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis HP hepatitis MESHD C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp MESHD, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/ AIDS MESHD drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B MESHD hepatitis HP B) for evaluation as inhibitors of SARS-CoV-2 RdRp MESHD. We demonstrated the ability of these three viral polymerase inhibitors, 3-fluoro-3-deoxythymidine triphosphate, 3-azido-3-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19.

    Nucleotide Analogues as Inhibitors of SARS-CoV Polymerase MESHD

    Authors: Jingyue Ju; Xiaoxu Li; Shiv Kumar; Steffen Jockusch; Minchen Chien; Chuanjuan Tao; Irina Morozova; Sergey Kalachikov; Robert Kirchdoerfer; James J. Russo

    doi:10.1101/2020.03.12.989186 Date: 2020-03-14 Source: bioRxiv

    SARS-CoV-2, a member of the coronavirus family, has caused a global public health emergency.1 Based on our analysis of hepatitis HP hepatitis MESHD C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved heptatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2.2 Here, using model polymerase extension experiments, we demonstrate that the activated triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV MESHD RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the activated triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase. Using the same molecular insight, we selected two other anti-viral agents, Alovudine and AZT (an FDA approved HIV/ AIDS MESHD drug) for evaluation as inhibitors of SARS-CoV RdRp MESHD. We demonstrate the ability of two HIV reverse transcriptase inhibitors, 3-fluoro-3-deoxythymidine triphosphate and 3-azido-3-deoxythymidine triphosphate (the active triphosphate forms of Alovudine and AZT), to be incorporated by SARS-CoV RdRp MESHD where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS-CoV and SARS-CoV-2 RdRps MESHD, we expect these nucleotide analogues would also inhibit the SARS-CoV-2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad-spectrum anti-coronavirus agents.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
The web page can also be accessed via API.

Sources


Annotations

All
None
MeSH Disease
Human Phenotype
Transmission
Seroprevalence


Export subcorpus as...

This service is developed in the project nfdi4health task force covid-19 which is a part of nfdi4health.

nfdi4health is one of the funded consortia of the National Research Data Infrastructure programme of the DFG.