Raoul Fioravanti
@uniroma1.it
Department of Chemistry
"Sapienza" University of Rome
Scopus Publications
Scopus Publications
Matteo Micucci, Silvia Gioacchini, Melissa Baggieri, Raoul Fioravanti, Paola Bucci, Roberto Giuseppetti, Srwa S. Saleem, Sazan Q. Maulud, Fuad O. Abdullah, Badr Q. Ismael,et al.
Elsevier BV
Melissa Baggieri, Silvia Gioacchini, Gigliola Borgonovo, Giorgia Catinella, Antonella Marchi, Pasquale Picone, Sonya Vasto, Raoul Fioravanti, Paola Bucci, Maedeh Kojouri,et al.
Elsevier BV
Matteo Biolatti, Marco Blangetti, Melissa Baggieri, Antonella Marchi, Silvia Gioacchini, Greta Bajetto, Davide Arnodo, Paola Bucci, Raoul Fioravanti, Maedeh Kojouri,et al.
American Chemical Society (ACS)
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.
Sara Cerra, Tommaso A. Salamone, Andrea Bearzotti, Farid Hajareh Haghighi, Martina Mercurio, Martina Marsotto, Chiara Battocchio, Raoul Fioravanti, Marco Diociaiuti, and Ilaria Fratoddi
Wiley
Alessandra Fraternale, Marta De Angelis, Riccardo De Santis, Donatella Amatore, Sofia Masini, Francesca Monittola, Michele Menotta, Federica Biancucci, Francesca Bartoccini, Michele Retini,et al.
Wiley
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.
Fabio Magurano, Matteo Micucci, Domenico Nuzzo, Melissa Baggieri, Pasquale Picone, Silvia Gioacchini, Raoul Fioravanti, Paola Bucci, Maedeh Kojouri, Michele Mari,et al.
Elsevier BV
Bruno Mattia Bizzarri, Angelica Fanelli, Stefania Ciprini, Alessandra Giorgi, Marta De Angelis, Raoul Fioravanti, Lucia Nencioni, and Raffaele Saladino
American Chemical Society (ACS)
Peptide nucleic acids (PNAs) play a key role in prebiotic chemistry as a chimera between RNA and proteins. We developed an alternative synthesis of bioactive PNA’s diaminopurine and guanine analogues from prebiotic compounds, such as aminomalononitrile (AMN), urea, and guanidine, using a two-step multicomponent microwave-assisted and solvent-free approach in the presence of selected amino acids. The novel derivatives showed selective inhibitory activity against influenza virus A/Puerto Rico/8/34 H1N1 encompassing the range of nanomolar activity. Derivatives decorated with the tyrosine residue showed the highest inhibitory activity against the virus.
Iole Venditti, Antonella Cartoni, Sara Cerra, Raoul Fioravanti, Tommaso Alberto Salamone, Fabio Sciubba, Maria Antonella Tabocchini, Valentina Dini, Chiara Battocchio, Giovanna Iucci,et al.
Wiley
Ilaria Fratoddi, Sara Cerra, Tommaso A. Salamone, Raoul Fioravanti, Fabio Sciubba, Emiliano Zampetti, Antonella Macagnano, Amanda Generosi, Barbara Paci, Francesca A. Scaramuzzo,et al.
American Chemical Society (ACS)
Laura Chronopoulou, Francesca A. Scaramuzzo, Raoul Fioravanti, Antonio di Nitto, Sara Cerra, Cleofe Palocci, and Ilaria Fratoddi
Elsevier BV
Enzyme immobilization on nanocarriers is nowadays considered a useful tool for improving activity and maintaining biocatalysts stability while facilitating their recovery and reuse. In this work we prepared Au and Ag based nanoparticles (AuNPs or AgNPs) stabilized with two different ligands, the organometallic dinuclear complex trans,trans-[dithiodibis(tributylphosphine)diplatinum(II)-4,4'-diethynylbiphenyl] (Pt-DEBP) and the organic dithiol 4,4'-dithiol-biphenyl (BI), able to link the NPs in 3D networks. We investigated the ability of these nanocarriers to interact with a model lipolytic enzyme from Pseudomonas fluorescens and maintain its activity, both in aqueous as well as in organic media. In particular, our results highlighted that the nature of the metal plays a role in enzyme adsorption, while enzyme activity is mostly influenced by the chemistry of the organic spacer. The obtained bioconjugate, between lipase and the most promising carrier, AgNPs-Pt-DEBP, was stable in a wide temperature range (25-55°C) and it showed good activity retention both in aqueous (50%) as well as in organic media (75%), compared to the lipase used in soluble form.
Marco Diociaiuti, Cecilia Bombelli, Laura Zanetti-Polzi, Marcello Belfiore, Raoul Fioravanti, Gianfranco Macchia, and Cristiano Giordani
MDPI AG
To investigate the interaction between amyloid assemblies and “lipid-rafts”, we performed functional and structural experiments on salmon calcitonin (sCT) solutions rich in prefibrillar oligomers, proto- and mature-fibers interacting with liposomes made of monosialoganglioside-GM1 (4%), DPPC (48%) and cholesterol (48%). To focus on the role played by electrostatic forces and considering that sCT is positive and GM1 is negative at physiologic pH, we compared results with those relative to GM1-free liposomes while, to assess membrane fluidity effects, with those relative to cholesterol-free liposomes. We investigated functional effects by evaluating Ca2+-influx in liposomes and viability of HT22-DIFF neurons. Only neurotoxic solutions rich in unstructured prefibrillar oligomers were able to induce Ca2+-influx in the “lipid-rafts” model, suggesting that the two phenomena were correlated. Thus, we investigated protein conformation and membrane modifications occurring during the interaction: circular dichroism showed that “lipid-rafts” fostered the formation of β-structures and energy filtered-transmission electron microscopy that prefibrillar oligomers formed pores, similar to Aβ did. We speculate that electrostatic forces between the positive prefibrillar oligomers and the negative GM1 drive the initial binding while the hydrophobic profile and flexibility of prefibrillar oligomers, together with the membrane fluidity, are responsible for the subsequent pore formation leading to Ca2+-influx and neurotoxicity.
Marcello Belfiore, Ida Cariati, Andrea Matteucci, Lucia Gaddini, Gianfranco Macchia, Raoul Fioravanti, Claudio Frank, Virginia Tancredi, Giovanna D’Arcangelo, and Marco Diociaiuti
Springer Science and Business Media LLC
Amyloid protein misfolding results in a self-assembling aggregation process, characterized by the formation of typical aggregates. The attention is focused on pre-fibrillar oligomers (PFOs), formed in the early stages and supposed to be neurotoxic. PFOs structure may change due to their instability and different experimental protocols. Consequently, it is difficult to ascertain which aggregation species are actually neurotoxic. We used salmon Calcitonin (sCT) as an amyloid model whose slow aggregation rate allowed to prepare stable samples without photochemical cross-linking. Intracellular Ca2+ rise plays a fundamental role in amyloid protein-induced neurodegerations. Two paradigms have been explored: (i) the “membrane permeabilization” due to the formation of amyloid pores or other types of membrane damage; (ii) “receptor-mediated” modulation of Ca2+ channels. In the present paper, we tested the effects of native sCT PFOs- with respect to Monomer-enriched solutions in neurons characterized by an increasing degree of differentiation, in terms of -Ca2+-influx, cellular viability, -Long-Term Potentiation impairment, Post-Synaptic Densities and synaptophysin expression. Results indicated that PFOs-, but not Monomer-enriched solutions, induced abnormal -Ca2+-influx, which could only in part be ascribed to NMDAR activation. Thus, we propose an innovative neurotoxicity mechanism for amyloid proteins where “membrane permeabilization” and “receptor-mediated” paradigms coexist.
Andrea Bearzotti, Paolo Papa, Antonella Macagnano, Emiliano Zampetti, Iole Venditti, Raoul Fioravanti, Laura Fontana, Roberto Matassa, Giuseppe Familiari, and Ilaria Fratoddi
Elsevier BV
Abstract Adsorption and detection of environmental total gaseous mercury (TGM) was studied by using gold nanoparticles (AuNPs) on purpose functionalized with dithiol ligands, i.e. Biphenyl-4,4′-dithiol (BI) or p-Terphenyl-4,4′′-dithiol (TR), suitable for nanoparticles based network formation. AuNPs-BI and AuNPs-TR with size 6–8 nm were deposited onto quartz fibres and used as adsorbent materials for the detection of TGM, both indoor for adsorption studies, at defined concentrations (∼4.5 ng m−3 Hg), and outdoor, at the vapour mercury concentration of the environmental countryside (∼1.5 ng m−3 Hg). The role of relative humidity (RH) in the absorption process has been observed. A high Hg adsorption capability, also when exposed to sub ppb concentration, has been observed. A cold vapour atomic fluorescence spectroscopy (CVAFS) detector was used to determine gaseous mercury concentrations lower than 2 ng m−3, with a robust and reproducible procedure. Moreover, the use of quartz fibres substrate covered with AuNPs-BI or AuNPs-TR, and used for more than thirty times during the experiments, makes them competitive in the use in large-scale measurement campaigns.