Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding. In aggregate, these results might help to define novel approaches to COVID-19 based on SARS-CoV-2 entry inhibitors

Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988–June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994–1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted

Notulae to the Italian native vascular flora: 11.

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions. A new combination in the genus Pilosella is proposed. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1

Interstitial lung diseases in a lung cancer screening trial

Interstitial lung diseases in a lung cancer screening trial are described usin C

A Multidisciplinary Study of Wild Grapevines in the River Crati Natural Reserve, South Italy (Calabria): Implications in Conservation Biology and Palaeoecological Reconstructions

Nowadays, wild grapevine populations are quite limited and sporadic mainly due to habitat destruction, land-use change, and the spread of pathogens that have reduced their distribution range. Palaeoecological, archaeobotanical, and genetic studies indicate that modern cultivars of Vitis vinifera are the results of the domestication of the dioecious, and sometimes hermaphrodite, wild species standing in riparian zones and wet environments. Wild grapevine populations have declined as a consequence of various forms of anthropogenic disturbance and were assigned by the IUCN Red List of Threatened Species to the Least Concern category. The River Crati Natural Reserve (Riserva Naturale Foce del Crati), located in southern Italy, hosts a population of Vitis vinifera subsp. sylvestris in a rewilding wet forest close to the Ionian Sea. These protected areas are of high scientific, biogeographic, and conservation interest in terms of Mediterranean biodiversity. Dendroecological and pollen morpho-biometric analyses of the wild grapevine are presented in this study. Palaeoecological perspectives for a landscape management strategy aimed at conserving and restoring the relic grapevine population are discussed

Interstitial lung diseases in a lung cancer screening trial

Purpose: To determine the prevalence and the evolution of interstitial lung disease (ILD) in a population of smokers included in a lung cancer screening trial. Methods and Materials: Two observers, blinded to any information, independently reviewed for the presence of ILD the low-dose thin-section CT scans of 692 consecutive heavy smokers (age ≥ 49 yrs, with ≥ 20 pack-years of smoking history) recruited by the Multicentric Italian Lung Detection (MILD) trial. The observers recorded the CT abnormalities and assigned a CT diagnosis of the disease. Subsequently, the observers evaluated the evolution of the abnormalities in the available CT scans obtained after three years. Results: In 158 out of 692 (22.8%) cases were recorded the presence of CT abnormalities consistent with ILD. In these cases, the CT diagnoses were respiratory bronchiolitis (RB)-like (109/692, 15.7%), nonspecific interstitial pneumonia (NSIP)-like (26/692, 3.8%), usual interstitial pneumonia (UIP)-like (2/698, 0.3%), and indeterminate (21/698, 3%). After three years, 40/44 (90.1%), 2/44 (4.5%), 2/44 (4.5%) RB-like cases and 9/14 (64.3%), 3/14 (21.4%), 2/14 (14.3%) NSIPlike cases showed no changes, an increase and a decrease in the extent of the abnormalities, respectively. Among the indeterminate CT diagnoses, the abnormalities remained stable, resolved and increased in 8/14 (57.2%), 4/14 (28.5%), 2/14 (14.3%) cases at follow‑up. Conclusion: Thin-section CT features of ILD, probably representing smokingrelated ILD, are not uncommon in a lung cancer screening population and should not be overlooked

Lessons from the wild: slow but increasing long-term growth allows for maximum longevity in European beech

This is the final paper: Piovesan, G., Biondi, F., Baliva, M., De Vivo, G., Marchianò, V., Schettino, A., & Di Filippo, A. (2019). Lessons from the wild: slow but increasing long‐term growth allows for maximum longevity in European beech. Ecology, 100(9), e02737. https://esajournals.onlinelibrary.wiley.com/doi/full/10.1002/ecy.2737