A green synthetic protocol to add a chemical function to a fully deprotected peptide to obtain a bioactive and/or fluorescent-labeled conjugate is reported. A range of S-conjugation reactions promoted by the commercially available LTA zeolite to introduce different substituents on peptide cysteine residues has been shown to take place in the solid state or in the presence of minimal amounts of organic solvent, with yields that are comparable to those of standard solution methods. The additional advantage of the procedure consists of easing the work up, for which green solvents, such as aqueous systems, can be employed. The protocol is implemented with microwave irradiation to shorten the reaction time as dielectric heating increases the diffusion rates of the mechanically milled reactants.
A microwave-assisted esterification reaction to prepare hyaluronan–curcumin derivatives by employing a solvent-free process was developed. In particular, a solid-state strategy to react two molecules characterized by totally different solubility profiles was developed. Hyaluronic acid, a highly hydrosoluble polysaccharide, was reacted with hydrophobic and even water-unstable curcumin. Microwave (MW) irradiation was employed to activate the reaction between the two solid compounds through the direct interaction with them and to preserve the integrity of the sensitive curcumin species. This new protocol can be considered efficient, fast, and also eco-friendly, avoiding the employment of toxic organic bases and solvents. A cytotoxicity test suggested that the developed hyaluronan–curcumin conjugate (HA-CUR) could be considered a candidate for its implementation as a new material. In addition, preliminary studies revealed promising anti-inflammatory activity and open future perspectives of further investigation.
Verdoliva V, Muzio G, Autelli R, Saviano M, Bedini E, De Luca S
The current coronavirus disease-2019 (COVID-19) pandemic is due to the novel coronavirus SARS-CoV-2. The scientific community has mounted a strong response by accelerating research and innovation, and has quickly set the foundation for understanding the molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key stage of the SARS-CoV-2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of the structural and functional data on the key actors of the replicatory machinery of SARS-CoV-2, to fill the gaps in the currently available structural data, which is mainly obtained through homology modeling. Moreover, learning from similar viruses, we collect data from the literature to reconstruct the pattern of interactions among the protein actors of the SARS-CoV-2 RNA polymerase machinery. Here, an important role is played by co-factors such as Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors that hold the entire machinery together to enhance the efficiency of RNA replication.
Here we report on the most recent updates on experimental drugs successfully employed
in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as
COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have
been reported after being treated with lopinavir/ritonavir (which is widely used to treat human
immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In
addition, remdesivir, which has been previously administered to Ebola virus patients, has also
proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine,
favipiravir and co-administered darunavir and umifenovir (in patient therapies)
were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths
ratio in the last weeks significantly increased, especially in China, it is clear that the experimental
antiviral therapy, together with the availability of intensive care unit beds in hospitals
and rigorous government control measures, all play an important role in dealing with this virus.
This also stresses the urgent need for the scientific community to devote its efforts to the
development of other more specific antiviral strategies.
The first outbreak of COVID-19 in Italy occurred during the second half of February 2020 in some areas in the North of the country. Due to the high contagiousness of the infection, further spread by asymptomatic people,
Italy has become in a few weeks the country with the greatest number of infected people in the world. The large number of severe cases among infected people in Italy led to the hospitalization of thousands of patients, with a heavy burden on the National Health Service.
Methods
We analyzed data provided daily by Italian Authorities for the period from 24 February 2020 to 30 March 2020. Considering such information, we developed a forecast model in real-time, based on the cumulative log-logistic distribution.
Results
A total of 101,739 infected individuals were confirmed until 30 March 2020, of which 14,620 recovered or discharged, and 11,591 deaths. Until the same date patients quarantined at home were 43,752, whereas hospitalized patients were 31,776, of which 3981 in intensive care. The active cases (i.e. the number of patients not yet recovered until that date) were 75,528. The forecast model estimated a number of infected persons for Italy of 234,000 about, and a duration of the epidemic of approximately 4 months.
Conclusions
One month after the first outbreaks there seemed to be the first signs of a decrease in the number of infections, showing that we could be now facing the descending phase of the epidemic. The forecast obtained thanks to our model could be used by decision-makers to implement coordinative and collaborative efforts in order to control the epidemic.
The pandemic due to novel Coronavirus must be a warning for all countries worldwide, regarding a rapid and complete dissemination of information, surveillance, health organization, and cooperation among the states.
In this manuscript, we describe a synthetic approach to a novel benzodifuran derivative as well as CD studies regarding its ability to interact with DNA and RNA. After the chemical synthesis and ESI-MS and NMR characterization, this heteroaromatic molecule was investigated by CD spectroscopy in order to evaluate it as a potential nucleic acid binder. Interestingly, the benzodifuran compound was found to be able to induce conformational changes in both DNA and RNA homoadenine molecules forming in the latter case a complex with a 6:1 benzodifuran/nucleobase stoichiometric ratio, as evidenced by CD titration experiments.
Chemical modifications of protein crystals may be achieved via soaking of reactants from their precipitating solution, through the solvent channel, into the protein matrix. We describe a Raman microscopy approach to follow mercury insertion into cysteine pairs within protein single crystals, via soaking in an aqueous Hg2+ solution. The method has been developed using bovine insulin as the model system. Applying an efficient mercuration protocol, consisting of a first step of disulphide bridge TCEP-induced reduction within the crystal, followed by overnight reaction with a HgCl2 solution, we obtained Hg-derivative crystals. Raman spectra collected on these derivative crystals, kept in the mother liquor, reveal a characteristic Raman band at 335 cm(-1), which has been assigned to a -S-Hg-S- bridge. The analysis provides Raman-based markers of mercury binding to cysteines, and thus of mercury intoxication.
This study directly compared the prognostic value of predischarge dobutamine stress echocardiography (DSE) and dobutamine myocardial SPECT perfusion imaging in patients with prior myocardial infarction. Methods: The study population consisted of 146 consecutive patients who underwent predischarge DSE and SPECT with 99mTc-sestamibi after a first acute uncomplicated myocardial infarction treated with thrombolysis. Fifty patients who underwent revascularization within 90 d from the imaging studies were excluded. Cardiac death and nonfatal myocardial infarction were considered events. Follow-up was 98% complete in a mean period of 44 ± 19 mo. Results: Myocardial ischemia was detectable in 55 (58%) patients at SPECT and in 63 (67%) patients at DSE. Concordance between SPECT and DSE in detecting ischemia was observed in 68 (72%) of the 94 patients (κ value, 0.41). During the follow-up, there were 20 cardiac events (9 deaths and 11 nonfatal myocardial infarctions). Ischemia at SPECT was a significant predictor of events (hazards ratio = 4.8; 95% confidence interval, 1.4-16.3; P < 0.01). However, ischemia at DSE (biphasic or worsening patterns) was not associated with events, whereas biphasic pattern alone was associated with a poor outcome compared with direct worsening (P < 0.05). Finally, at Cox multivariate analysis, ischemia at SPECT but not biphasic pattern at DSE was a significant independent predictor of events (P < 0.01). Conclusion: These results indicate that, after uncomplicated myocardial infarction, ischemia at SPECT is associated with an increased risk of cardiac events at long-term follow-up. However, ischemia at DSE was unable to stratify patients after myocardial infarction.
L'Istituto di Biostrutture e Bioimmagini (IBB) del Consiglio Nazionale delle Ricerche (CNR) ha 100 unità di personale distribuite nelle sedi di Napoli e Torino (70 ricercatori/tecnologi) e svolge attività di ricerca traslazionale per lo sviluppo nuovi strumenti per la prevenzione, la diagnosi e terapie a bersaglio molecolare.
Per realizzare questi obiettivi ricercatori che studiano le biomolecole da un punto di vista strutturale e funzionale collaborano con esperti di imaging preclinico che studiano modelli cellulari ed animali di malattie umane e ricercatori clinici che effettuano sperimentazioni nell'uomo.
Le attività di ricerca comprendono la ricerca di base, un laboratorio per l’Imaging preclinico dei piccoli animali da laboratorio ed aree di ricerca clinica svolte in collaborazione con Università ed altri enti di ricerca. La combinazione di competenze inerenti la chimica teorica e la progettazione e la sperimentazione, sia in vitro che in vivo, di nuovi agenti diagnostici e terapeutici con le competenze in molteplici modalità di imaging (tra cui MRI, imaging ottico, PET / SPECT, ecografia, TC) forniscono le basi interdisciplinari per realizzare una ricerca innovativa nel campo dell'imaging molecolare e della terapia personalizzata.
Un altro settore di ricerca sviluppato dall’IBB è rappresentato dall’e-Health. L’attività ha lo scopo di realizzare sistemi software open-source, costituiti da modelli, servizi e strumenti di supporto alla diagnosi, terapia e follow-up, nonché per la gestione innovativa dei processi sanitari.
L'Istituto fa parte del nodo italiano del Forum strategico europeo sulle infrastrutture di ricerca denominato EuroBioimaging (EuBi). EuBi è una large-scale facility a livello pan-europeo in grado di fornire a ricercatori provenienti da tutta Europa il libero accesso alle più innovative tecnologie di imaging biologico e medicale.
L’attività fondamentale dell’Istituto di Biostrutture e Bioimmagini è costituita dalle seguenti aree di ricerca:
• Design, sintesi, espressione e caratterizzazione strutturale di molecole di interesse biologico, e loro interazioni con ioni metallici. Applicazioni in campo diagnostico e terapeutico.
• Tecnologie biochimiche e biostrutture;
• Tecnologie biochimiche finalizzate alla diagnostica per immagini;
• Diagnostica per immagini e radioterapia;
• Imaging molecolare preclinico e clinico. Nuovi agenti diagnostici/teragnostici per Imaging Molecolare;
• Sviluppo di soluzioni tecnologiche innovative di e-health, con particolare attenzione alla tematiche della telemedicina e della diagnosi assistita.