Characterization of RNA G-quadruplexes in porcine epidemic diarrhea virus genome and the antiviral activity of G-quadruplex ligands

Article Multidisciplinary Sciences

RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection

Geng Liu et al.

Summary: RNA G-quadruplex structure plays a crucial role in SARS-CoV-2 infection by inhibiting TMPRSS2 translation and preventing viral entry, making it a potential target for COVID-19 prevention and treatment.

NATURE COMMUNICATIONS (2022)

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Article Chemistry, Medicinal

Targeting the RNA G-Quadruplex and Protein Interactome for Antiviral Therapy

Li-Yan Zhai et al.

Summary: In recent years, G-quadruplexes (G4s) have been found in many harmful viruses, and G4 ligands have been designed to target these structures, showing promising antiviral effects. This perspective summarizes the diverse roles of RNA G4s in different viruses, introduces small-molecule ligands developed as G4 modulators, and reviews the medical intervention of G4-interacting proteins from both the virus and the host. The challenges and opportunities in G4-based antiviral therapy are also discussed.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Review Biochemistry & Molecular Biology

Recent advances in applying G-quadruplex for SARS-CoV-2 targeting and diagnosis: A review

Li-Yan Zhai et al.

Summary: This article summarizes the recent progress and intervention methods of SARS-CoV-2 G4s, and introduces the potential interacting proteins related to G4. In addition, it discusses the innovative strategy of using G4s as a diagnostic tool for SARS-CoV-2 detection, and raises some key questions that need to be addressed in the future.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2022)

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Article Cell Biology

RNA G-quadruplex formed in SARS-CoV-2 used for COVID-19 treatment in animal models

Geng Qin et al.

Summary: The study reveals the presence of highly conservative and stable G-quadruplexes (G4s) in SARS-CoV-2, which play a dual role in inhibiting viral replication and transcription processes. The cationic porphyrin compound TMPyP4, targeting SARS-CoV-2 G4s, shows excellent antiviral activity and effectively suppresses SARS-CoV-2 infection in animal models. This research provides a novel therapeutic approach by targeting the secondary structures within the SARS-CoV-2 genome and opens new possibilities for the design of selective drug candidates.

CELL DISCOVERY (2022)

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Article Biochemistry & Molecular Biology

SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules

Yi Zheng et al.

Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Chemistry, Multidisciplinary

Targeting RNA G-Quadruplex in SARS-CoV-2: A Promising Therapeutic Target for COVID-19?

Chuanqi Zhao et al.

Summary: Researchers found that specific sequences in the SARS-CoV-2 genome can form G4 structures, and their biofunctions can be regulated by specific compounds, providing new insights for developing novel antiviral drugs against COVID-19.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Review Biochemistry & Molecular Biology

G-Quadruplexes in RNA Biology: Recent Advances and Future Directions

Leila Dumas et al.

Summary: RNA G-quadruplexes (RG4s) are four-stranded structures that control gene expression mechanisms and play a significant role in cellular processes and disease development. Current research focuses on the transient conformation of RG4s, their interaction with RNA modifications, role in cell compartmentalization, and impact on host immune response. RG4-binding proteins are highlighted as key determinants of their conformation and biological functions.

TRENDS IN BIOCHEMICAL SCIENCES (2021)

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Article Immunology

SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species

Mehdi Moustaqil et al.

Summary: The study revealed that the proteases NSP3 and NSP5 of SARS-CoV-2 can cleave proteins involved in host immune responses, shedding light on the mechanisms behind enhanced inflammatory responses in COVID-19 patients. The direct cleavage of specific proteins by these proteases provides insights into the pathophysiology of the disease.

EMERGING MICROBES & INFECTIONS (2021)

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Article Medicine, Research & Experimental

Inhibition of Zika virus replication by G-quadruplex-binding ligands

Prativa Majee et al.

Summary: Research identified potential non-canonical G-quadruplex structures in the Zika virus genome, which can be targeted by ligands like Braco-19 and TMPyP4 to inhibit virus replication and protein production.

MOLECULAR THERAPY-NUCLEIC ACIDS (2021)

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Article Biochemical Research Methods

Success of prophylactic antiviral therapy for SARS-CoV-2: Predicted critical efficacies and impact of different drug-specific mechanisms of action

Peter Czuppon et al.

Summary: Repurposed drugs play a key role in the defense against new viral infections, preventing viral infection and reducing the risk of infection. Combination drug therapy can lower the infection risk, particularly by blocking viral entry into cells or increasing viral clearance. Prophylactic antiviral therapy is crucial for healthcare workers and high-risk populations in preventing viral infections.

PLOS COMPUTATIONAL BIOLOGY (2021)

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Article Virology

G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets

Yance Zhu et al.

Summary: This study identified two novel G4-forming sequences, OriL-A and OriL-S, in the PRV genome, which can fold into parallel G4 structures in vitro. Treatment of PRV-infected cells with the G4 stabilizer PhenDC3 significantly inhibited PRV DNA replication in host cells, without affecting PRV attachment and entry. These findings suggest that G4 may serve as an innovative therapeutic target against PRV.

VIRUSES-BASEL (2021)

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Article Cell Biology

Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CLpro substrate degradome

Isabel Pablos et al.

Summary: Research on the main viral protease of SARS-CoV-2 and its relationship with human protein substrates has revealed a large group of substrates, accelerating the exploration of pathophysiology and drug design. The study also demonstrates the interactions between 3CL(pro) and the Hippo pathway and other key effector proteins in human cells.

CELL REPORTS (2021)

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Article Biochemistry & Molecular Biology

SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction

Marc Lavigne et al.

Summary: The study revealed that the SARS-CoV-2 Nsp3 protein contains a SUD domain that interacts with G4s, which can be disrupted by preventing G4 structures from forming or using specific ligands. This opens up possibilities for further research on the role of SUD/G4 interactions in SARS-CoV-2 replication and the development of inhibitors as potential antiviral compounds.

NUCLEIC ACIDS RESEARCH (2021)

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Review Veterinary Sciences

Porcine enteric coronaviruses: an updated overview of the pathogenesis, prevalence, and diagnosis

Qiang Liu et al.

Summary: Porcine enteric coronaviruses (PECs) infections have had a serious impact on pig health and the pig industry's economy, requiring urgent attention.

VETERINARY RESEARCH COMMUNICATIONS (2021)

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Article Virology

Two Inhibitors Against the 3C-Like Proteases of Swine Coronavirus and Feline Coronavirus

Mengxin Zhou et al.

Summary: This study identified two compounds that target the 3C-like protease (3CL(pro)) of porcine epidemic diarrhoea virus (PEDV) and exhibit antiviral capacity against feline infectious peritonitis virus (FIPV). These compounds may aid in the development of anti-coronavirus drugs in the future.

VIROLOGICA SINICA (2021)

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Review Cell Biology