Valentina Riva

Trichothiodystrophy-causative pathogenic variants impair a cooperative action of TFIIH and DDX1 in R-loop processing

Debora Ferri, Giulia Branca, Manuela Lanzafame, Erica Gandolfi et autres

The transcription factor IIH (TFIIH) is a key player in transcription and DNA repair by nucleotide excision repair. It is made of 10 subunits organized in core-TFIIH and CAK sub-complexes bridged by XPD. Pathogenic variants in the ERCC2/XPD gene give rise to …

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Synergistic action of human RNaseH2 and the RNA helicase-nuclease DDX3X in processing R-loops

Massimiliano Secchi, Anna Garbelli, Valentina Riva, Graziano Deidda et autres

R-loops are three-stranded RNA-DNA hybrid structures that play important regulatory roles, but excessive or deregulated R-loops formation can trigger DNA damage and genome instability. Digestion of R-loops is mainly relying on the action of two specialized ribonucleases: RNaseH1 and RNaseH2. RNaseH2 is …

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Targeting DDX3X Helicase Activity with BA103 Shows Promising Therapeutic Effects in Preclinical Glioblastoma Models

Annalaura Brai, Valentina Riva, Letizia Clementi, Lucia Falsitta et autres

DDX3X is an ATP-dependent RNA helicase that has recently attracted interest for its involvement in viral replication and oncogenic progression. Starting from hit compounds previously identified by our group, we have designed and synthesized a new series of DDX3X inhibitors that effectively …

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Epidemiology of neuronal surface antibody-mediated autoimmune encephalitis and antibody-based diagnostics

Luigi Zuliani, Sabrina Marangoni, Piera De Gaspari, Irene Rosellini et autres

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Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases

Valentina Riva, Anna Garbelli, Federica Casiraghi, Francesca Arena et autres

Removal of ribonucleotides (rNMPs) incorporated into the genome by the ribonucleotide excision repair (RER) is essential to avoid genetic instability. In eukaryotes, the RNaseH2 is the only known enzyme able to incise 5' of the rNMP, starting the RER process, which is …

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Novel Insights into the Biochemical Mechanism of CK1ε and its Functional Interplay with DDX3X

Bartolo Bono, Giulia Franco, Valentina Riva, Anna Garbelli et autres

Casein Kinase 1 epsilon (CK1ε) is a member of the serine (Ser)/threonine (Thr) CK1 family, known to have crucial roles in several biological scenarios and, ever more frequently, in pathological contexts, such as cancer. Recently, the human DEAD-box RNA helicase 3 X-linked …

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Unique Domain for a Unique Target: Selective Inhibitors of Host Cell DDX3X to Fight Emerging Viruses

Valentina Riva, Anna Garbelli, Annalaura Brai, Federica Casiraghi et autres

Emerging viruses like dengue, West Nile, chikungunya, and Zika can cause widespread viral epidemics. Developing novel drugs or vaccines against specific targets for each virus is a difficult task. As obligate parasites, all viruses exploit common cellular pathways, providing the possibility to …

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DDX3X inhibitors, an effective way to overcome HIV-1 resistance targeting host proteins

Annalaura Brai, Valentina Riva, Francesco Saladini, Claudio Zamperini et autres

The huge resources that had gone into Human Immunodeficiency virus (HIV) research led to the development of potent antivirals able to suppress viral load in the majority of treated patients, thus dramatically increasing the life expectancy of people living with HIV. However, …

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Exploring the Implication of DDX3X in DENV Infection: Discovery of the First-in-Class DDX3X Fluorescent Inhibitor

Annalaura Brai, Adele Boccuto, Martina Monti, Serena Marchi et autres

In the absence of effective drugs or vaccines for the treatment of the five Dengue Virus serotypes, the search for novel antiviral drugs is of primary importance for the scientific community. In this context, drug repurposing represents the most used strategy; however, …

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Antiviral potential coupled to genome stability: the multifaceted roles of DDX3X

Valentina Riva

Synthesis and Antiviral Activity of Novel 1,3,4-Thiadiazole Inhibitors of DDX3X

Annalaura Brai, Stefania Ronzini, Valentina Riva, Lorenzo Botta et autres

The human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against both infectious diseases and cancer. Herein, a new family of DDX3X inhibitors was designed, synthesized, and tested for its inhibitory action on the …

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From the Magic Bullet to the Magic Target: Exploiting the Diverse Roles of DDX3X in Viral Infections and Tumorigenesis

Valentina Riva, Giovanni Maga

DDX3X is an ATPase/RNA helicase of the DEAD-box family and one of the most multifaceted helicases known up to date, acting in RNA metabolism, cell cycle control, apoptosis, stress response and innate immunity. Depending on the virus or the viral cycle stage, …

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