Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses.
Jiarui Li,Ester Boix +1 more
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TLDR
In this article, the authors summarize the currently available information on human RNases that can target viral pathogens, with special focus on enveloped single-stranded RNA (ssRNA) viruses.Abstract:
Owing to the recent outbreak of Coronavirus Disease of 2019 (COVID-19), it is urgent to develop effective and safe drugs to treat the present pandemic and prevent other viral infections that might come in the future. Proteins from our own innate immune system can serve as ideal sources of novel drug candidates thanks to their safety and immune regulation versatility. Some host defense RNases equipped with antiviral activity have been reported over time. Here, we try to summarize the currently available information on human RNases that can target viral pathogens, with special focus on enveloped single-stranded RNA (ssRNA) viruses. Overall, host RNases can fight viruses by a combined multifaceted strategy, including the enzymatic target of the viral genome, recognition of virus unique patterns, immune modulation, control of stress granule formation, and induction of autophagy/apoptosis pathways. The review also includes a detailed description of representative enveloped ssRNA viruses and their strategies to interact with the host and evade immune recognition. For comparative purposes, we also provide an exhaustive revision of the currently approved or experimental antiviral drugs. Finally, we sum up the current perspectives of drug development to achieve successful eradication of viral infections.read more
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References
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Soluble factors from T cells inhibiting X4 strains of HIV are a mixture of β chemokines and RNases
Fiorenza Cocchi,Anthony L. DeVico,Wuyuan Lu,Mikulas Popovic,Olga Latinovic,Mohammad M. Sajadi,Robert R. Redfield,Mark K. Lafferty,Massimo Galli,Alfredo Garzino-Demo,Robert C. Gallo +10 more
TL;DR: These HIV X4-suppressive factors are identified primarily as a mixture of three β chemokines and two RNases of lesser potency and show that in a clade B population, some correlate with clinical status and are produced by both CD4+ and CD8+ T cells (chemokines, angiogenin, and RNase 4).
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TL;DR: Cryo-electron microscopy is used to determine a three-dimensional structure of an HIV-1 RT initiation complex and illustrates how RNA structure in the initiation complex alters RT conformation to decrease activity, highlighting a potential target for drug action.
Journal ArticleDOI
Structure and activity of the only human RNase T2
Andrea Thorn,Robert Steinfeld,M. Ziegenbein,Marcel Grapp,He-Hsuan Hsiao,Henning Urlaub,George M. Sheldrick,Jutta Gärtner,Ralph Krätzner +8 more
TL;DR: The X-ray structure of human RNase T2 is determined at 1.6 Å resolution and shows high similarity to those of known T2 RNase structures from plants, while, in contrast, the external loop regions show distinct structural differences.
Journal ArticleDOI
RNase L Amplifies Interferon Signaling by Inducing Protein Kinase R-Mediated Antiviral Stress Granules.
TL;DR: A role during viral infection is proposed for RNase L-cleaved RNAs in inducing avSGs containing antiviral proteins to provide a platform for efficient interaction of RNA ligands with pattern recognition receptors to enhance IFN production to mount an effective antiviral response.
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Three decades of antiviral drugs
TL;DR: Thirty years ago, just three drugs were available for the treatment of viral infections, but now more than forty have been approved and what might the future hold for antiviral drug development?
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