In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

AbstractCOVID-19 has currently become the biggest challenge in the world. There is still no specific medicine for COVID-19, which leaves a critical gap for the identification of new drug candidates for the disease. Recent studies have reported that the small-molecule enoxacin exerts an antiviral activity by enhancing the RNAi pathway. The aim of this study is to analyze if enoxacin can exert anti-SARS-CoV-2 effects. We exploit multiple computational tools and databases to examine (i) whether the RNAi mechanism, as the target pathway of enoxacin, could act on the SARS-CoV-2 genome, and (ii) microRNAs induced by enoxacin might directly silence viral components as well as the host cell proteins mediating the viral entry and replication. We find that the RNA genome of SARS-CoV-2 might be a suitable substrate for DICER activity. We also highlight several enoxacin-enhanced microRNAs which could target SARS-CoV-2 components, pro-inflammatory cytokines, host cell components facilitating viral replication, and transcription factors enriched in lung stem cells, thereby promoting their differentiation and lung regeneration. Finally, our analyses identify several enoxacin-targeted regulatory modules that were critically associated with exacerbation of the SARS-CoV-2 infection. Overall, our analysis suggests that enoxacin could be a promising candidate for COVID-19 treatment through enhancing the RNAi pathway.

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In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

10.21203/rs.3.rs-96308/v1 ◽

2020 ◽

Author(s):

Amirhossein Ahmadi ◽

Sharif Moradi

Keyword(s):

Host Cell ◽

Viral Entry ◽

In Silico Analysis ◽

Rnai Pathway ◽

Drug Candidates ◽

Critical Gap ◽

Host Cell Proteins ◽

Cell Components ◽

Viral Components ◽

Lung Regeneration

Abstract COVID-19 has currently become the biggest challenge in the world. There is still no specific medicine for COVID-19, which leaves a critical gap for the identification of new drug candidates for the disease. Recent studies have reported that the small-molecule enoxacin exerts an antiviral activity by enhancing the RNAi pathway. The aim of this study is to analyze if enoxacin can exert anti-SARS-CoV-2 effects. We exploit multiple computational tools and databases to examine (i) whether the RNAi mechanism, as the target pathway of enoxacin, could act on the SARS-CoV-2 genome, and (ii) microRNAs induced by enoxacin might directly silence viral components as well as the host cell proteins mediating the viral entry and replication. We find that the RNA genome of SARS-CoV-2 is a suitable substrate for DICER activity. We also highlight several enoxacin-enhanced microRNAs which could target SARS-CoV-2 components, pro-inflammatory cytokines, host cell components facilitating viral replication, and transcription factors enriched in lung stem cells, thereby promoting their differentiation and lung regeneration. Finally, our analyses identify several enoxacin-targeted regulatory modules that were critically associated with exacerbation of the SARS-CoV-2 infection. Overall, our analysis suggests that enoxacin could be a promising candidate for COVID-19 treatment through enhancing the RNAi pathway.

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Targeting viral entry as a strategy for broad-spectrum antivirals

F1000Research ◽

10.12688/f1000research.19694.1 ◽

2019 ◽

Vol 8 ◽

pp. 1628 ◽

Cited By ~ 15

Author(s):

Michela Mazzon ◽

Mark Marsh

Keyword(s):

Life Cycle ◽

Host Cell ◽

Viral Entry ◽

Broad Spectrum ◽

Host Cell Proteins

The process of entry into a host cell is a key step in the life cycle of most viruses. In recent years, there has been a significant increase in our understanding of the routes and mechanisms of entry for a number of these viruses. This has led to the development of novel broad-spectrum antiviral approaches that target host cell proteins and pathways, in addition to strategies focused on individual viruses or virus families. Here we consider a number of these approaches and their broad-spectrum potential.

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Precision analysis for the determination of steric mass action parameters using eight tobacco host cell proteins

Journal of Chromatography A ◽

10.1016/j.chroma.2021.462379 ◽

2021 ◽

pp. 462379

Author(s):

C.R. Bernau ◽

R.C. Jäpel ◽

J.W. Hübbers ◽

S. Nölting ◽

P. Opdensteinen ◽

...

Keyword(s):

Host Cell ◽

Mass Action ◽

Precision Analysis ◽

Host Cell Proteins

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Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures

Viruses ◽

10.3390/v13050784 ◽

2021 ◽

Vol 13 (5) ◽

pp. 784

Author(s):

Solène Lerolle ◽

Natalia Freitas ◽

François-Loïc Cosset ◽

Vincent Legros

Keyword(s):

Host Cell ◽

Viral Entry ◽

Current Knowledge ◽

Restriction Factors ◽

Antiviral State ◽

Cellular Factors ◽

Pathogenic Viruses ◽

Genome Transcription ◽

Infected Cells ◽

Molecular Patterns

The Bunyavirales order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune system that aims at inhibiting viral replication and propagation. Upon recognition of pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs), numerous signaling cascades are activated, leading to the production of interferons (IFNs). IFNs act in an autocrine and paracrine manner to establish an antiviral state by inducing the expression of hundreds of IFN-stimulated genes (ISGs). Some of these ISGs are known to restrict bunyavirus infection. Along with other constitutively expressed host cellular factors with antiviral activity, these proteins (hereafter referred to as “restriction factors”) target different steps of the viral cycle, including viral entry, genome transcription and replication, and virion egress. In reaction to this, bunyaviruses have developed strategies to circumvent this antiviral response, by avoiding cellular recognition of PAMPs, inhibiting IFN production or interfering with the IFN-mediated response. Herein, we review the current knowledge on host cellular factors that were shown to restrict infections by bunyaviruses. Moreover, we focus on the strategies developed by bunyaviruses in order to escape the antiviral state developed by the infected cells.

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Modulation of Autophagy by SARS-CoV-2: A Potential Threat for Cardiovascular System

Frontiers in Physiology ◽

10.3389/fphys.2020.611275 ◽

2020 ◽

Vol 11 ◽

Author(s):

Puneet Kaur Randhawa ◽

Kaylyn Scanlon ◽

Jay Rappaport ◽

Manish K. Gupta

Keyword(s):

Host Cell ◽

Rna Virus ◽

Clinical Manifestations ◽

Cardiovascular Complications ◽

Extracellular Proteases ◽

Potential Threat ◽

Surface Receptors ◽

Drug Candidates ◽

A Genome ◽

Number Of Patients

Recently, we have witnessed an unprecedented increase in the number of patients suffering from respiratory tract illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus is a single-stranded positive-sense RNA virus with a genome size of ~29.9 kb. It is believed that the viral spike (S) protein attaches to angiotensin converting enzyme 2 cell surface receptors and, eventually, the virus gains access into the host cell with the help of intracellular/extracellular proteases or by the endosomal pathway. Once, the virus enters the host cell, it can either be degraded via autophagy or evade autophagic degradation and replicate using the virus encoded RNA dependent RNA polymerase. The virus is highly contagious and can impair the respiratory system of the host causing dyspnea, cough, fever, and tightness in the chest. This disease is also characterized by an abrupt upsurge in the levels of proinflammatory/inflammatory cytokines and chemotactic factors in a process known as cytokine storm. Certain reports have suggested that COVID-19 infection can aggravate cardiovascular complications, in fact, the individuals with underlying co-morbidities are more prone to the disease. In this review, we shall discuss the pathogenesis, clinical manifestations, potential drug candidates, the interaction between virus and autophagy, and the role of coronavirus in exaggerating cardiovascular complications.

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