Molecular investigation on measles cases rise and variants co-circulation in the Lazio region, Italy Cesare Ernesto Maria Gruber, Silvia Gioacchini, Lavinia Fabeni, Martina Rueca, Licia Bordi, Eleonora Lalle, Melissa Baggieri, Paola Bucci, Raoul Fioravanti, Roberto Giuseppetti, Eliana Specchiarello, Pietro Giorgio Spezia, Giulia Berno, Fabrizio Carletti, Gabriella De Carli, Maria Concetta Fusco, Alessandra Barca, Paola Scognamiglio, Antonella Marchi, Emilio D’Ugo, Enrico Girardi, Francesco Vairo, Fabio Magurano, Fabrizio Maggi Virology Journal, 2025 PURPOSE: In 2023-2024, measles cases progressively increased in Europe. Multiple outbreaks were reported and viral strains with three-nucleotide mutations potentially compromising diagnostic testing were identified. We analyzed the first cases of measles reported in Lazio (Central Italy) from September 2023 to March 2024, combining molecular characterization and phylogenetic analysis with epidemiological investigation to identify transmission chains and evaluate the sensitivity of PCR tests adopted on circulating viral strains. METHODS: We tested samples collected through routine measles and rubella surveillance for IgM, IgG and Real-Time PCR. We sequenced positive samples with higher viral titers using an amplicon-based whole-genome next-generation sequencing (WG-NGS) approach and performed mutational and phylogenetic analysis. Furthermore, we tested the sensitivity of the PCR molecular diagnostic assay adopted in our laboratory to identify the mutated strains. RESULTS: Of the 39 suspected cases, 28 were confirmed. Endemic cases were 82%; of these, 78% were sporadic at epidemiological investigation. From 21 high-titer samples, we obtained 14 strains belonging to the D8 genotype. Phylogenetic analysis identified four distinct clusters: three associating 50% of sporadic cases, and one confirming the epidemiological investigation. Several mutational patterns were identified, one of which had three nucleotide mutations potentially affecting the diagnostic test. However, our routine diagnostic PCR tests are able to detect mutated strains at different dilutions. CONCLUSION: Our results demonstrate that WG-NGS can be used to distinguish transmission chains and identify infection clusters to improve surveillance activity and enable the implementation of more targeted control measures, highlighting the importance of integrated epidemiological and genomic surveillance.
From multiple measles genotype D8 introductions in 2024 to sustained B3 local transmission in and around Milan, northern Italy, January to April 2025 Clara Fappani, Maria Gori, Silvia Bianchi, Lucia Tieghi, Daniela Colzani, Sabrina Senatore, Marino Faccini, Priscilla Pasutto, Luca Imeri, Luigi Vezzosi, Gabriele Del Castillo, Simone Villa, Danilo Cereda, Silvia Gioacchini, Paola Bucci, Raoul Fioravanti, Emilio D’Ugo, Melissa Baggieri, Fabio Magurano, Antonella Amendola Eurosurveillance, 2025 An outbreak of measles virus genotype B3 is ongoing in Milan and surrounding areas since February 2025, with 27 cases identified in 32 laboratory-confirmed measles cases. Most cases were locally acquired and young adults. Phylogenetic analysis indicated the presence of a unique lineage closely related to strains circulating in Morocco. The lack of epidemiological links between several affected individuals suggests case numbers are being underestimated. The continuous transmission raises concerns about the potential re-establishment of endemic circulation in northern Italy.
Molecular mechanisms at the basis of the protective effect exerted by EPPS on neurodegeneration induced by prefibrillar amyloid oligomers Beatrice Zarrilli, Roberto Bonanni, Marcello Belfiore, Mariagrazia Severino, Ida Cariati, Raoul Fioravanti, Giacomo Cappella, Simona Sennato, Claudio Frank, Cristiano Giordani, Virginia Tancredi, Cecilia Bombelli, Marco Diociaiuti, Giovanna D’Arcangelo Scientific Reports, 2024 It has been shown recently, without an explanation of the possible molecular mechanisms involved, that 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic (EPPS) acid effectively protects from the neurotoxicity induced by oligomers and plaques formed by the protein amyloid-β protein. Here we report the same protective effect, obtained in vitro (HT22-diff cell line) and ex vivo (hippocampal slices) models, against amyloid neurotoxicity induced by oligomers of salmon Calcitonin (sCT), which has been shown to be a good model for the study of neurodegenerative diseases. Based on biophysical studies focusing on the protein aggregation kinetic and the interaction of the aggregates with model membranes, we propose a possible molecular mechanism underlying the protective effects. Taken together, our results indicate that EPPS is able to counteract the direct association (primary aggregation) of harmless low-molecular weight aggregates (dimers and trimers) or their aggregation catalysed by surfaces present in the solution (secondary aggregation). Thus, EPPS stabilizes harmless aggregates and hinders the formation of toxic and metastable prefibrillar oligomers. Overall, our data demonstrate that EPPS is an excellent drug candidate for the treatment of neurodegeneration due to misfolded proteins, such as Alzheimer's or Parkinson's disease.
Review from host and guest approach to new frontiers nutraceuticals in the era of COVID-19 Matteo Micucci, Silvia Gioacchini, Melissa Baggieri, Raoul Fioravanti, Paola Bucci, Roberto Giuseppetti, Srwa S. Saleem, Sazan Q. Maulud, Fuad O. Abdullah, Badr Q. Ismael, Jivan Q. Ahmed, Emilio D'Ugo, Antonella Marchi, Udodinma Jude Okeke, Fabio Magurano Future Foods, 2024 COVID-19 continues to claim victims in the world, especially among elderly subjects and people suffering from chronic-degenerative pathologies, like cardiovascular diseases. Several vaccines and drugs have been developed to mitigate the infection spread and its deleterious consequences. However, the emergence of new variants requires the identification of solutions to deal with the challenging mutations. In this context, the investigation of phytocomplexes and related compounds used in folk medicine and culinary purposes may lead to unfold nutraceuticals endowed with antiviral, and cardioprotective properties. We have described several vegetal extracts and secondary metabolites that hit the most important viral and host targets and bind them. The connection between SARS-CoV-2 and cardiovascular diseases were also outlined, as well as phytocomplexes with potentials for their mitigation. The review provides both an entry point for new researchers in this area, and a comprehensive overview for further investigation of the natural products presented.
The BETTER Project: Development of a tool for the measurement of SARS-CoV-2 via Internet of Medical Things POCT Fiore Capasso, Rosalba Pitruzzella, Ines Tavoletta, Chiara Perri, Luigi Zeni, Giovanni Porto, Francesco Arcadio, Alessandro Chiodi, Chiara Marzano, Luca Pasquale Renzullo, Raoul Fioravanti, Domenico Del Prete, Silvia Gioacchini, Fabio Magurano, Nunzio Cennamo 2024 IEEE Sensors Applications Symposium Sas 2024 Proceedings, 2024 An Internet of Medical Things (IoMT) sensor system was proposed to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More specifically, a disposable sensor chip is realized by using a modified plastic optical fiber in order to excite the Surface Plasmon Resonance phenomenon useful to monitor the interaction between a specific molecularly imprinted polymer and the spike of SARS-CoV-2. The disposable chip is integrated into a portable and small-size system with a light source and a spectrometer to make the measurements at the patients' place, so a point of care test (POCT) connected to the Internet is realized. The acquired data are processed using a developed Windows-based application, and a dedicated software architecture was designed and implemented. This latter consists of a server in the cloud, a database, and a website. The proposed IoMT-POCT was developed and tested during the BETTER Project via approximately 1,000 positive and negative nasopharyngeal swabs in a universal transport medium. The results obtained through this sensor system were compared with those obtained using a gold-standard technique. A further potential of the proposed sensor system is the possibility of automatically performing a statistical analysis of the data provided, which is reported on the website.
Antiviral, virucidal and antioxidant properties of Artemisia annua against SARS-CoV-2 Melissa Baggieri, Silvia Gioacchini, Gigliola Borgonovo, Giorgia Catinella, Antonella Marchi, Pasquale Picone, Sonya Vasto, Raoul Fioravanti, Paola Bucci, Maedeh Kojouri, Roberto Giuseppetti, Emilio D’Ugo, Fausto Ubaldi, Sabrina Dallavalle, Domenico Nuzzo, Andrea Pinto, Fabio Magurano Biomedicine and Pharmacotherapy, 2023 Natural products are a rich source of bioactive molecules that have potential pharmacotherapeutic applications. In this study, we focused on Artemisia annua (A. annua) and its enriched extracts which were biologically evaluated in vitro as virucidal, antiviral, and antioxidant agents, with a potential application against the COVID-19 infection. The crude extract showed virucidal, antiviral and antioxidant effects in concentrations that did not affect cell viability. Scopoletin, arteannuin B and artemisinic acid (single fractions isolated from A. annua) exerted a considerable virucidal and antiviral effect in vitro starting from a concentration of 50 µg/mL. Data from Surface Plasmon Resonance (SPR) showed that the inhibition of the viral infection was due to the interaction of these compounds with the 3CLpro and Spike proteins of SARS-CoV-2, suggesting that the main interaction of compounds may interfere with the viral pathways during the insertion and the replication process. The present study suggests that natural extract of A. annua and its components could have a key role as antioxidants and antiviral agents and support the fight against SARS-CoV-2 variants and other possible emerging Coronaviruses.
Strigolactones as Broad-Spectrum Antivirals against β-Coronaviruses through Targeting the Main Protease Mpro Matteo Biolatti, Marco Blangetti, Melissa Baggieri, Antonella Marchi, Silvia Gioacchini, Greta Bajetto, Davide Arnodo, Paola Bucci, Raoul Fioravanti, Maedeh Kojouri, Matteo Bersani, Giulia D’Arrigo, Lydia Siragusa, Simone Ghinato, Marco De Andrea, Francesca Gugliesi, Camilla Albano, Selina Pasquero, Ivan Visentin, Emilio D’Ugo, Francesca Esposito, Paolo Malune, Enzo Tramontano, Cristina Prandi, Francesca Spyrakis, Fabio Magurano, Valentina Dell’Oste ACS Infectious Diseases, 2023 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, in silico simulations suggest the binding of SLs in the SARS-CoV-2 main protease (Mpro) active site, and this was further confirmed by an in vitro activity assay. Overall, our results highlight the potential efficacy of SLs as broad-spectrum antivirals against β-coronaviruses, which may provide the rationale for repurposing this class of hormones for the treatment of COVID-19 patients.
Thiol-Functionalized Palladium Nanoparticles Networks: Synthesis, Characterization, and Room Temperature (Toxic) Vapor Detection Sara Cerra, Tommaso A. Salamone, Andrea Bearzotti, Farid Hajareh Haghighi, Martina Mercurio, Martina Marsotto, Chiara Battocchio, Raoul Fioravanti, Marco Diociaiuti, Ilaria Fratoddi Particle and Particle Systems Characterization, 2023 Abstract The preparation of three different functionalized palladium nanoparticles (PdNPs) systems for room temperature BTX (benzene, toluene, p‐xylene) sensing detection and their morphostructural characterization is described. PdNPs are prepared through a two‐phase water/toluene wet chemical reduction method in the presence of bifunctional organic thiols as stabilizing agents suitable for the formation of covalently linked PdNPs networks: p ‐terphenyl‐4,4″‐dithiol (PdNPs‐TR), biphenyl‐4,4′‐dithiol (PdNPs‐BP), or with 9,9‐didodecyl‐2,7‐bis(acetylthio)fluorene (PdNPs‐FL). Comparing the hydrodynamic diameter values, TR and BP ligands help to obtain networks consisting of spherical NPs of about 2 nm, in which each bifunctional ligand act as a bridge between PdNPs. In contrast, PdNPs‐FL show a population centered at <2R H > = 45 ± 5 nm. To perform preliminary gas sensing measurements, PdNPs networks are cast deposited on interdigitated electrodes to study their resistive response toward volatile organic compounds (VOCs) such as benzene (0–5%), toluene (0–1.7%), and p ‐xylene (0–0.4%) (BTX) and common interfering gases (H 2 S, NH 3 , SO 2 , and relative humidity, RH). PdNPs‐FL show enhanced response to BTX with an appreciable response also toward H 2 S and RH. PdNPs‐TR exhibit a better ability to discriminate benzene gas with a negligible response after H 2 S exposure. Moreover, all the PdNPs systems show little to no response to NH 3 and SO 2 gases, offering an interesting perspective in practical sensing applications.
Targeting SARS-CoV-2 by synthetic dual-acting thiol compounds that inhibit Spike/ACE2 interaction and viral protein production Alessandra Fraternale, Marta De Angelis, Riccardo De Santis, Donatella Amatore, Sofia Masini, Francesca Monittola, Michele Menotta, Federica Biancucci, Francesca Bartoccini, Michele Retini, Valentina Fiori, Raoul Fioravanti, Fabio Magurano, Laura Chiarantini, Romano F. Lista, Giovanni Piersanti, Anna T. Palamara, Lucia Nencioni, Mauro Magnani, Rita Crinelli FASEB Journal, 2023 The SARS-CoV-2 life cycle is strictly dependent on the environmental redox state that influences both virus entry and replication. A reducing environment impairs the binding of the spike protein (S) to the angiotensin-converting enzyme 2 receptor (ACE2), while a highly oxidizing environment is thought to favor S interaction with ACE2. Moreover, SARS-CoV-2 interferes with redox homeostasis in infected cells to promote the oxidative folding of its own proteins. Here we demonstrate that synthetic low molecular weight (LMW) monothiol and dithiol compounds induce a redox switch in the S protein receptor binding domain (RBD) toward a more reduced state. Reactive cysteine residue profiling revealed that all the disulfides present in RBD are targets of the thiol compounds. The reduction of disulfides in RBD decreases the binding to ACE2 in a cell-free system as demonstrated by enzyme-linked immunosorbent and surface plasmon resonance (SPR) assays. Moreover, LMW thiols interfere with protein oxidative folding and the production of newly synthesized polypeptides in HEK293 cells expressing the S1 and RBD domain, respectively. Based on these results, we hypothesize that these thiol compounds impair both the binding of S protein to its cellular receptor during the early stage of viral infection, as well as viral protein folding/maturation and thus the formation of new viral mature particles. Indeed, all the tested molecules, although at different concentrations, efficiently inhibit both SARS-CoV-2 entry and replication in Vero E6 cells. LMW thiols may represent innovative anti-SARS-CoV-2 therapeutics acting directly on viral targets and indirectly by inhibiting cellular functions mandatory for viral replication.
A potential host and virus targeting tool against COVID-19: Chemical characterization, antiviral, cytoprotective, antioxidant, respiratory smooth muscle relaxant effects of Paulownia tomentosa Steud Fabio Magurano, Matteo Micucci, Domenico Nuzzo, Melissa Baggieri, Pasquale Picone, Silvia Gioacchini, Raoul Fioravanti, Paola Bucci, Maedeh Kojouri, Michele Mari, Michele Retini, Roberta Budriesi, Laura Beatrice Mattioli, Ivan Corazza, Valentina Di Liberto, Luigi Todaro, Roberto Giuseppetti, Emilio D’Ugo, Antonella Marchi, Marisabel Mecca, Maurizio D’Auria Biomedicine and Pharmacotherapy, 2023 COronaVIrus Disease 2019 (COVID-19) is a newly emerging infectious disease that spread across the world, caused by the novel coronavirus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Despite the advancements in science that led to the creation of the vaccine, there is still an urgent need for new antiviral drugs effective against SARS-CoV-2. This study aimed to investigate the antiviral effect of Paulownia tomentosa Steud extract against SARS-CoV-2 and to evaluate its antioxidant properties, including respiratory smooth muscle relaxant effects. Our results showed that P. tomentosa extract can inhibit viral replication by directly interacting with both the 3-chymotrypsin-like protease and spike protein. In addition, the phyto complex does not reduce lung epithelial cell viability and exerts a protective action in those cells damaged by tert-butyl hydroperoxide , a toxic agent able to alter cells' functions via increased oxidative stress. These data suggest the potential role of P. tomentosa extract in COVID-19 treatment, since this extract is able to act both as an antiviral and a cytoprotective agent in vitro.
Hydrophilic Gold Nanoparticles as Anti-PD-L1 Antibody Carriers: Synthesis and Interface Properties Iole Venditti, Antonella Cartoni, Sara Cerra, Raoul Fioravanti, Tommaso Alberto Salamone, Fabio Sciubba, Maria Antonella Tabocchini, Valentina Dini, Chiara Battocchio, Giovanna Iucci, Laura Carlini, Riccardo Faccini, Francesco Collamati, Carlo Mancini Terracciano, Elena Solfaroli Camillocci, Silvio Morganti, Alessandro Giordano, Teresa Scotognella, Daria Maccora, Dante Rotili, Cinzia Marchese, Eleni Anastasiadou, Pankaj Trivedi, Ilaria Fratoddi Particle and Particle Systems Characterization, 2022
Functionalized Gold Nanoparticles as an Active Layer for Mercury Vapor Detection at Room Temperature Ilaria Fratoddi, Sara Cerra, Tommaso A. Salamone, Raoul Fioravanti, Fabio Sciubba, Emiliano Zampetti, Antonella Macagnano, Amanda Generosi, Barbara Paci, Francesca A. Scaramuzzo, Roberto Matassa, Giuseppe Familiari, Chiara Battocchio, Martina Marsotto, Paolo Papa, Andrea Bearzotti ACS Applied Nano Materials, 2021
