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  1. Article: Antiherpetic Activity of a Root Exudate from

    Bajetto, Greta / Arnodo, Davide / Biolatti, Matteo / Trifirò, Linda / Albano, Camilla / Pasquero, Selina / Gugliesi, Francesca / Campo, Eva / Spyrakis, Francesca / Prandi, Cristina / De Andrea, Marco / Dell'Oste, Valentina / Visentin, Ivan / Blangetti, Marco

    Microorganisms

    2024  Volume 12, Issue 2

    Abstract: The rise of drug resistance to antivirals poses a significant global concern for public health; therefore, there is a pressing need to identify novel compounds that can effectively counteract strains resistant to current antiviral treatments. In light of ...

    Abstract The rise of drug resistance to antivirals poses a significant global concern for public health; therefore, there is a pressing need to identify novel compounds that can effectively counteract strains resistant to current antiviral treatments. In light of this, researchers have been exploring new approaches, including the investigation of natural compounds as alternative sources for developing potent antiviral therapies. Thus, this work aimed to evaluate the antiviral properties of the organic-soluble fraction of a root exudate derived from the tomato plant
    Language English
    Publishing date 2024-02-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms12020373
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: PAD-mediated citrullination is a novel candidate diagnostic marker and druggable target for HPV-associated cervical cancer.

    Albano, Camilla / Biolatti, Matteo / Mazibrada, Jasenka / Pasquero, Selina / Gugliesi, Francesca / Lo Cigno, Irene / Calati, Federica / Bajetto, Greta / Riva, Giuseppe / Griffante, Gloria / Landolfo, Santo / Gariglio, Marisa / De Andrea, Marco / Dell'Oste, Valentina

    Frontiers in cellular and infection microbiology

    2024  Volume 14, Page(s) 1359367

    Abstract: Citrullination is an emerging post-translational modification catalyzed by peptidyl-arginine deiminases (PADs) that convert peptidyl-arginine into peptidyl-citrulline. In humans, the PAD family consists of five isozymes (PADs 1-4, 6) involved in multiple ...

    Abstract Citrullination is an emerging post-translational modification catalyzed by peptidyl-arginine deiminases (PADs) that convert peptidyl-arginine into peptidyl-citrulline. In humans, the PAD family consists of five isozymes (PADs 1-4, 6) involved in multiple diseases, including cancer. Given that high-risk (hr) human papillomaviruses (HPVs) are the etiological agents of cervical cancer, in this study, we sought to determine whether PAD-mediated protein citrullination would play a functional role in the HPV-driven transformation of epithelial cells. Here we show that both total protein citrullination and PAD4 expression levels are significantly associated with cervical cancer progression. Specifically, epithelial immunostaining for PAD4 revealed an increasingly higher histoscore from low-grade (CIN1) to high-grade (CIN2, CIN3) cervical intraepithelial neoplasia, and invasive squamous cell carcinoma (SCC) lesions, raising the attractive possibility that PAD4 may be used as tumor staging markers. Furthermore, taking advantage of the epidermoid cervical cancer cell line CaSki, which harbors multiple copies of the integrated HPV16 genome, we show that the expression of E6 and E7 HPV oncoproteins is impaired by treatment with the pharmacological pan-PAD inhibitor BB-Cl-amidine. Consistently, p53 and p21, two targets of HPV oncoproteins, are upregulated by the PAD inhibitor, which undergoes cell growth arrest and apoptosis. Altogether, these findings highlight a novel mechanism by which hrHPVs alter host regulatory pathways involved in cell cycle and survival to gain viral fitness, raising the possibility that PADs may represent an attractive target for developing novel host-targeting antivirals effective in preventing cervical cancer progression.
    MeSH term(s) Female ; Humans ; Citrullination ; Uterine Cervical Neoplasms ; Papillomavirus Infections ; Papillomavirus E7 Proteins/genetics ; Carcinoma, Squamous Cell ; Arginine
    Chemical Substances Papillomavirus E7 Proteins ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2024-03-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2024.1359367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Antimicrobial Efficacy of a Vegetable Oil Plasticizer in PVC Matrices.

    Bajetto, Greta / Scutera, Sara / Menotti, Francesca / Banche, Giuliana / Chiaradia, Giuseppe / Turesso, Caterina / De Andrea, Marco / Vallino, Marta / Van Es, Daan S / Biolatti, Matteo / Dell'Oste, Valentina / Musso, Tiziana

    Polymers

    2024  Volume 16, Issue 8

    Abstract: The growing prevalence of bacterial and viral infections, highlighted by the recent COVID-19 pandemic, urgently calls for new antimicrobial strategies. To this end, we have synthesized and characterized a novel fatty acid epoxy-ester plasticizer for ... ...

    Abstract The growing prevalence of bacterial and viral infections, highlighted by the recent COVID-19 pandemic, urgently calls for new antimicrobial strategies. To this end, we have synthesized and characterized a novel fatty acid epoxy-ester plasticizer for polymers, named GDE. GDE is not only sustainable and user-friendly but also demonstrates superior plasticizing properties, while its epoxy components improve the heat stability of PVC-based matrices. A key feature of GDE is its ability to confer antimicrobial properties to surfaces. Indeed, upon contact, this material can effectively kill enveloped viruses, such as herpes simplex virus type 1 (HSV-1) and the β-coronavirus prototype HCoV-OC43, but it is ineffective against nonenveloped viruses like human adenovirus (HAdV). Further analysis using transmission electron microscopy (TEM) on HSV-1 virions exposed to GDE showed significant structural damage, indicating that GDE can interfere with the viral envelope, potentially causing leakage. Moreover, GDE demonstrates antibacterial activity, albeit to a lesser extent, against notorious pathogens such as
    Language English
    Publishing date 2024-04-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527146-5
    ISSN 2073-4360 ; 2073-4360
    ISSN (online) 2073-4360
    ISSN 2073-4360
    DOI 10.3390/polym16081046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Citrullination profile analysis reveals peptidylarginine deaminase 3 as an HSV-1 target to dampen the activity of candidate antiviral restriction factors.

    Pasquero, Selina / Gugliesi, Francesca / Biolatti, Matteo / Dell'Oste, Valentina / Albano, Camilla / Bajetto, Greta / Griffante, Gloria / Trifirò, Linda / Brugo, Bianca / Raviola, Stefano / Lacarbonara, Davide / Yang, Qiao / Sudeshna, Sen / Barasa, Leonard / Haniff, Hafeez / Thompson, Paul R / Landolfo, Santo / De Andrea, Marco

    PLoS pathogens

    2023  Volume 19, Issue 12, Page(s) e1011849

    Abstract: Herpes simplex virus 1 (HSV-1) is a neurotropic virus that remains latent in neuronal cell bodies but reactivates throughout an individual's life, causing severe adverse reactions, such as herpes simplex encephalitis (HSE). Recently, it has also been ... ...

    Abstract Herpes simplex virus 1 (HSV-1) is a neurotropic virus that remains latent in neuronal cell bodies but reactivates throughout an individual's life, causing severe adverse reactions, such as herpes simplex encephalitis (HSE). Recently, it has also been implicated in the etiology of Alzheimer's disease (AD). The absence of an effective vaccine and the emergence of numerous drug-resistant variants have called for the development of new antiviral agents that can tackle HSV-1 infection. Host-targeting antivirals (HTAs) have recently emerged as promising antiviral compounds that act on host-cell factors essential for viral replication. Here we show that a new class of HTAs targeting peptidylarginine deiminases (PADs), a family of calcium-dependent enzymes catalyzing protein citrullination, exhibits a marked inhibitory activity against HSV-1. Furthermore, we show that HSV-1 infection leads to enhanced protein citrullination through transcriptional activation of three PAD isoforms: PAD2, PAD3, and PAD4. Interestingly, PAD3-depletion by specific drugs or siRNAs dramatically inhibits HSV-1 replication. Finally, an analysis of the citrullinome reveals significant changes in the deimination levels of both cellular and viral proteins, with the interferon (IFN)-inducible proteins IFIT1 and IFIT2 being among the most heavily deiminated ones. As genetic depletion of IFIT1 and IFIT2 strongly enhances HSV-1 growth, we propose that viral-induced citrullination of IFIT1 and 2 is a highly efficient HSV-1 evasion mechanism from host antiviral resistance. Overall, our findings point to a crucial role of citrullination in subverting cellular responses to viral infection and demonstrate that PAD inhibitors efficiently suppress HSV-1 infection in vitro, which may provide the rationale for their repurposing as HSV-1 antiviral drugs.
    MeSH term(s) Humans ; Herpesvirus 1, Human/physiology ; Citrullination ; Antiviral Restriction Factors ; Herpes Simplex ; Viral Proteins/metabolism ; Virus Replication ; Antiviral Agents/pharmacology ; Antiviral Agents/metabolism
    Chemical Substances Antiviral Restriction Factors ; Viral Proteins ; Antiviral Agents
    Language English
    Publishing date 2023-12-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011849
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Novel antiviral activity of PAD inhibitors against human beta-coronaviruses HCoV-OC43 and SARS-CoV-2.

    Pasquero, Selina / Gugliesi, Francesca / Griffante, Gloria / Dell'Oste, Valentina / Biolatti, Matteo / Albano, Camilla / Bajetto, Greta / Delbue, Serena / Signorini, Lucia / Dolci, Maria / Landolfo, Santo / De Andrea, Marco

    Antiviral research

    2022  Volume 200, Page(s) 105278

    Abstract: The current SARS-CoV-2 pandemic, along with the likelihood that new coronavirus strains will appear in the nearby future, highlights the urgent need to develop new effective antiviral agents. In this scenario, emerging host-targeting antivirals (HTAs), ... ...

    Abstract The current SARS-CoV-2 pandemic, along with the likelihood that new coronavirus strains will appear in the nearby future, highlights the urgent need to develop new effective antiviral agents. In this scenario, emerging host-targeting antivirals (HTAs), which act on host-cell factors essential for viral replication, are a promising class of antiviral compounds. Here we show that a new class of HTAs targeting peptidylarginine deiminases (PADs), a family of calcium-dependent enzymes catalyzing protein citrullination, is endowed with a potent inhibitory activity against human beta-coronaviruses (HCoVs). Specifically, we show that infection of human fetal lung fibroblasts with HCoV-OC43 leads to enhanced protein citrullination through transcriptional activation of PAD4, and that inhibition of PAD4-mediated citrullination with either of the two pan-PAD inhibitors Cl-A and BB-Cl or the PAD4-specific inhibitor GSK199 curbs HCoV-OC43 replication. Furthermore, we show that either Cl-A or BB-Cl treatment of African green monkey kidney Vero-E6 cells, a widely used cell system to study beta-CoV replication, potently suppresses HCoV-OC43 and SARS-CoV-2 replication. Overall, our results demonstrate the potential efficacy of PAD inhibitors, in suppressing HCoV infection, which may provide the rationale for the repurposing of this class of inhibitors for the treatment of COVID-19 patients.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; Cell Line ; Chlorocebus aethiops ; Coronavirus OC43, Human ; Humans ; SARS-CoV-2 ; COVID-19 Drug Treatment
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2022-03-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2022.105278
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection.

    Griffante, Gloria / Hewelt-Belka, Weronika / Albano, Camilla / Gugliesi, Francesca / Pasquero, Selina / Castillo Pacheco, Sergio Fernando / Bajetto, Greta / Porporato, Paolo Ettore / Mina, Erica / Vallino, Marta / Krapp, Christian / Jakobsen, Martin Roelsgaard / Purdy, John / von Einem, Jens / Landolfo, Santo / Dell'Oste, Valentina / Biolatti, Matteo

    mBio

    2022  Volume 13, Issue 3, Page(s) e0043522

    Abstract: Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection, as increased lipogenesis in HCMV-infected cells favors the envelopment of newly synthesized viral particles. As all cells are equipped with restriction factors (RFs) ...

    Abstract Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection, as increased lipogenesis in HCMV-infected cells favors the envelopment of newly synthesized viral particles. As all cells are equipped with restriction factors (RFs) able to exert a protective effect against invading pathogens, we asked whether a similar defense mechanism would also be in place to preserve the metabolic compartment from HCMV infection. Here, we show that gamma interferon (IFN-γ)-inducible protein 16 (IFI16), an RF able to block HCMV DNA synthesis, can also counteract HCMV-mediated metabolic reprogramming in infected primary human foreskin fibroblasts (HFFs), thereby limiting virion infectivity. Specifically, we find that IFI16 downregulates the transcriptional activation of the glucose transporter 4 (GLUT4) through cooperation with the carbohydrate-response element-binding protein (ChREBP), thereby reducing HCMV-induced transcription of lipogenic enzymes. The resulting decrease in glucose uptake and consumption leads to diminished lipid synthesis, which ultimately curbs the
    MeSH term(s) Cellular Reprogramming ; Cytomegalovirus/physiology ; Cytomegalovirus Infections ; DNA, Viral/genetics ; Fibroblasts ; Humans ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Virus Replication
    Chemical Substances DNA, Viral ; Nuclear Proteins ; Phosphoproteins ; IFI16 protein, human (148998-64-5)
    Language English
    Publishing date 2022-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00435-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Strigolactones as Broad-Spectrum Antivirals against β-Coronaviruses through Targeting the Main Protease M

    Biolatti, Matteo / Blangetti, Marco / Baggieri, Melissa / Marchi, Antonella / Gioacchini, Silvia / Bajetto, Greta / Arnodo, Davide / Bucci, Paola / Fioravanti, Raoul / Kojouri, Maedeh / Bersani, Matteo / D'Arrigo, Giulia / Siragusa, Lydia / Ghinato, Simone / De Andrea, Marco / Gugliesi, Francesca / Albano, Camilla / Pasquero, Selina / Visentin, Ivan /
    D'Ugo, Emilio / Esposito, Francesca / Malune, Paolo / Tramontano, Enzo / Prandi, Cristina / Spyrakis, Francesca / Magurano, Fabio / Dell'Oste, Valentina

    ACS infectious diseases

    2023  Volume 9, Issue 7, Page(s) 1310–1318

    Abstract: The current SARS-CoV-2 pandemic and the likelihood that new coronavirus strains will emerge in the immediate future point out the urgent need to identify new pan-coronavirus inhibitors. Strigolactones (SLs) are a class of plant hormones with multifaceted ...

    Abstract The current SARS-CoV-2 pandemic and the likelihood that new coronavirus strains will emerge in the immediate future point out the urgent need to identify new pan-coronavirus inhibitors. Strigolactones (SLs) are a class of plant hormones with multifaceted activities whose roles in plant-related fields have been extensively explored. Recently, we proved that SLs also exert antiviral activity toward herpesviruses, such as human cytomegalovirus (HCMV). Here we show that the synthetic SLs TH-EGO and EDOT-EGO impair β-coronavirus replication including SARS-CoV-2 and the common cold human coronavirus HCoV-OC43. Interestingly,
    MeSH term(s) Humans ; COVID-19 ; Antiviral Agents/pharmacology ; Antiviral Agents/chemistry ; SARS-CoV-2 ; Peptide Hydrolases
    Chemical Substances Antiviral Agents ; GR24 strigolactone ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2023-06-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.3c00219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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