CRISPR Tackles Emerging Viral Pathogens

Kirby, Emily N; Shue, Byron; Thomas, Paul Q.; Beard, Michael R.

doi:10.3390/v13112157

Cited by 7 publications

(9 citation statements)

References 151 publications

(180 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some CRISPR systems have been developed to detect nucleic acids or pathogen biomarkers. CRISPR-based biosensing platforms are expected to revolutionize the diagnosis of pathogens [ 17 , 18 ]. The field of CRISPR system exploration is growing rapidly.…”

Section: Introductionmentioning

confidence: 99%

Application of CRISPR/Cas Systems in the Nucleic Acid Detection of Infectious Diseases

Wang

et al. 2022

Diagnostics

View full text Add to dashboard Cite

The CRISPR/Cas system is a protective adaptive immune system against attacks from foreign mobile genetic elements. Since the discovery of the excellent target-specific sequence recognition ability of the CRISPR/Cas system, the CRISPR/Cas system has shown excellent performance in the development of pathogen nucleic-acid-detection technology. In combination with various biosensing technologies, researchers have made many rapid, convenient, and feasible innovations in pathogen nucleic-acid-detection technology. With an in-depth understanding and development of the CRISPR/Cas system, it is no longer limited to CRISPR/Cas9, CRISPR/Cas12, and other systems that had been widely used in the past; other CRISPR/Cas families are designed for nucleic acid detection. We summarized the application of CRISPR/Cas-related technology in infectious-disease detection and its development in SARS-CoV-2 detection.

show abstract

Section: Introductionmentioning

confidence: 99%

Application of CRISPR/Cas Systems in the Nucleic Acid Detection of Infectious Diseases

Wang

et al. 2022

Diagnostics

View full text Add to dashboard Cite

show abstract

“…The above steps might allow to lower the probability of the appearance of resistance mutations, and would potentially still allow natural ligands to interact with the endogenous target protein. Complete inhibition of a specific host target function required for viral spreading is also possible and would mirror gene knock out of host dependency factors, as exemplified in studies using the CRISPR technology (Kirby et al, 2021; Li et al, 2020; Watanabe et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Structural basis for targeting the human T-cell leukemia virus Tax oncoprotein and syntenin-1 interaction using a small molecule

Maseko

Molle

Blibek

et al. 2021

Preprint

View full text Add to dashboard Cite

SUMMARYHuman T-cell leukemia virus type-1 (HTLV-1) is the first pathogenic retrovirus discovered in human. Although HTLV-1-induced diseases are well characterized and linked to the encoded Tax-1 protein, there is currently no strategy to target Tax-1 functions with small molecules. Here, we report a comprehensive interaction map between Tax-1 and human PDZ domain-containing proteins (hPDZome), and we show that Tax-1 interacts with one-third of them. This includes proteins involved in cell cycle, cell-cell junction and cytoskeleton organization, as well as in membrane complexes assembly. Using nuclear magnetic resonance (NMR) spectroscopy, we have determined the structural basis of the interaction between the C-terminal PDZ binding motif (PBM) of Tax-1, and the PDZ domains of DLG1 and syntenin-1. Finally, we have used molecular modeling and mammalian cell-based assays to demonstrate that Tax-1/PDZ-domain interactions are amenable to small-molecule inhibition. Thus, our work provides a framework for the design of targeted therapies for HTLV-1-induced diseases.Highlightscomprehensive interactome map of HTLV-1 Tax / human PDZ proteinsbasis of Tax-1 PBM binding to human DLG1 and syntenin-1 PDZ domains”.significance of inhibiting Tax-1 functionsof the Tax-1 / PDZ interfaceGraphical abstract

show abstract

“…Therefore, combined and/or integrative approaches together with functional characterization are necessary to validate the biological relevance of any potential novel HDF that might be putatively developed as HDT. This section provides a brief overview on the fundamentals of the distinct approaches (extensively reviewed elsewhere (6)(7)(8)(9)(10)(11)(12)(13), with special focus on their key strengths and weaknesses, and comparing and contrasting the three screening approaches for elucidating host-virus interactions that may ultimately lead to HDT.…”

Section: Identification Of Host Dependency Factorsmentioning

confidence: 99%

“…Usually, once CRISPR KO is performed, KO cells undergo a functional readout through virus infection followed by a selection process due to virus-induced cell death. The surviving cells are then collected for KO characterization analysis (11,13,26). Of note, potential silencing of genes essential for cell survival and growth hampers the study of their role as HDF and arose as one of the limitations of the CRISPR-KO screening studies, besides to the large-scale readout requirements.…”

Section: Crispr-cas9 Knock-out Screeningmentioning

confidence: 99%

“…Recently, optimization of CRISPR system using Cas12 instead of Cas9, allowed the development of an alternative PAM, which targets T'-rich gene sequences (29). Moreover, gene editing is expanding to other applications as for example the direct silencing of mRNA using the class VI CRISPR/Cas13 systems which hybridizes and cleaves directly the target RNA without the requirement for a PAM sequence (30), as an alternative to siRNA (13).…”

Section: Crispr-cas9 Knock-out Screeningmentioning

confidence: 99%

See 1 more Smart Citation

Viral-Host Dependency Factors as Therapeutic Targets to Overcome Antiviral Drug-Resistance: A Focus on Innate Immune Modulation

Badía

García-Vidal²,

Ballana³

2022

Front. Virol.

View full text Add to dashboard Cite

The development of antiviral drugs, has provided enormous achievements in our recent history in the fight against viral infections. To date, most of the approved antiviral drugs target virus-encoded proteins to achieve direct antiviral activity. Nonetheless, the inherent idiosyncrasy of viral mutations during their replication cycle, enable many viruses to adapt to the new barriers, becoming resistant to therapies, therefore, representing an ever-present menace and prompting the scientific community towards the development of novel therapeutic strategies. Taking advantage of the increasing knowledge of virus-host cell interactions, the targeting of cellular factors or pathways essential for virus survival turns into an alternative strategy to intervene in almost every step of viral replication cycle. Since host factors are evolutionary conserved, viral evasion to host-directed therapies (HDT) would impose a higher genetic barrier to the emergence of resistant strains. Thus, targeting host factors has long been considered an alternative strategy to overcome viral resistance. Nevertheless, targeting host factors or pathways potentially hints undesired off targets effects, and therefore, a critical risk-benefit evaluation is required. The present review discusses the current state-of-the-art on the identification of viral host dependency factors (HDF) and the workflow required for the development of HDT as antivirals. Then, we focus on the feasibility of using a specific class of host factors, those involved in innate immune modulation, as broad-spectrum antiviral therapeutic strategies. Finally, a brief summary of major roadblocks derived from targeting host cellular proteins and putative future strategies to overcome its major limitations is proposed.

show abstract

CRISPR Tackles Emerging Viral Pathogens

Cited by 7 publications

References 151 publications

Application of CRISPR/Cas Systems in the Nucleic Acid Detection of Infectious Diseases

Application of CRISPR/Cas Systems in the Nucleic Acid Detection of Infectious Diseases

Structural basis for targeting the human T-cell leukemia virus Tax oncoprotein and syntenin-1 interaction using a small molecule

Viral-Host Dependency Factors as Therapeutic Targets to Overcome Antiviral Drug-Resistance: A Focus on Innate Immune Modulation

Contact Info

Product

Resources

About