Interaction of Pelargonium sidoides Compounds with Lactoferrin and SARS-CoV-2: Insights from Molecular Simulations.

(1) Background: Pelargonium sidoides extracts and lactoferrin are two important natural, anti-inflammatory, and antiviral agents, which can interfere with the early stages of SARS-CoV-2 infection. Molecular docking and molecular dynamics simulation approaches have been applied to check for the occurrence of interactions of the Pelargonium sidoides compounds with lactoferrin and with SARS-CoV-2 components. (2) Methods: Computational methods have been applied to confirm the hypothesis of a direct interaction between PEL compounds and the lactoferrin protein and between Pelargonium sidoides compounds and SARS-CoV-2 Spike, 3CLPro, RdRp proteins, and membrane. Selected high-score complexes were structurally investigated through classical molecular dynamics simulation, while the interaction energies were evaluated using the molecular mechanics energies combined with generalized Born and surface area continuum solvation method. (3) Results: Computational analyses suggested that Pelargonium sidoides extracts can interact with lactoferrin without altering its structural and dynamical properties. Furthermore, Pelargonium sidoides compounds should have the ability to interfere with the Spike glycoprotein, the 3CLPro, and the lipid membrane, probably affecting the functional properties of the proteins inserted in the double layer. (4) Conclusion: Our findings suggest that Pelargonium sidoides may interfere with the mechanism of infection of SARS-CoV-2, especially in the early stages.

Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences.

Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 µg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients.

Indoor air quality at school and students' performance: Recommendations of the UNESCO Chair on Health Education and Sustainable Development & the Italian Society of Environmental Medicine (SIMA).

The issue of indoor air quality (IAQ) concerns 64 million students across Europe, but it is still a neglected topic, although it impacts both their health and learning outcomes. Classroommicroclimate is the first key factor determining a healthy or unhealthy school environment, and it is influenced by ventilation, temperature and humidity rate. Classrooms are usually crowded, overheated and poorly ventilated, thus resulting in possible increases of carbon dioxide (CO2), that can cause several problems when its concentrations exceed the value of 0.15 percentage volume of CO2 (1500 ppm) or even at lower levels (1000 ppm). CO2 can also arise from outside the school, being widely produced by the combustion of fossils or road traffic. Anthropogenic activities are responsible for the emission of nitrogen dioxide (NO2) and polycyclic aromatic hydrocarbons(PAH) too, which represent other possible external contaminants potentially impairing IAQ. Furtherdangerous exposures for students' health are those related to natural emission of gas Radon, which typically accumulates in poorly ventilated classrooms, and volatile organic compounds (VOCs, released by building materials, paints, furnishings, detergents), while chemicals substances (i.e.cyanoacrylate, lead, cadmium, nickel) might be contained in school materials. Finally, particulate matter (PM2.5 and PM10) originating from road traffic, domestic heating or industrial activities represent additional possible contaminants impacting schools' air quality. Poor IAQ might result in mild adverse events (i.e. headaches, nausea etc.) or cause respiratory problems. More frequently, IAQ affects students' attention and their school performances, as widely documented by many studies. Standardized tests administered to pupils exposed to poor IAQ (to assess reading and mathematical abilities) systematically result in worse outcomes compared to students staying in healthy classroom environments. In this paper, we present recommendations of UNESCO Chair on Health Education and Sustainable Development and Italian Society of Environmental Medicine(SIMA) to ensure an optimal IAQ at school, including some post-COVID-19 issues.

Searching for SARS-COV-2 on Particulate Matter: A Possible Early Indicator of COVID-19 Epidemic Recurrence.

A number of nations were forced to declare a total shutdown due to COVID-19 infection, as extreme measure to cope with dramatic impact of the pandemic, with remarkable consequences both in terms of negative health outcomes and economic loses. However, in many countries a "Phase-2" is approaching and many activities will re-open soon, although with some differences depending on the severity of the outbreak experienced and SARS-COV-2 estimated diffusion in the general population. At the present, possible relapses of the epidemic cannot be excluded until effective vaccines or immunoprophylaxis with human recombinant antibodies will be properly set up and commercialized. COVD-19-related quarantines have triggered serious social challenges, so that decision makers are concerned about the risk of wasting all the sacrifices imposed to the people in these months of quarantine. The availability of possible early predictive indicators of future epidemic relapses would be very useful for public health purposes, and could potentially prevent the suspension of entire national economic systems. On 16 March, a Position Paper launched by the Italian Society of Environmental Medicine (SIMA) hypothesized for the first time a possible link between the dramatic impact of COVID-19 outbreak in Northern Italy and the high concentrations of particulate matter (PM10 and PM2.5) that characterize this area, along with its well-known specific climatic conditions. Thereafter, a survey carried out in the U.S. by the Harvard School of Public Health suggested a strong association between increases in particulate matter concentration and mortality rates due to COVID-19. The presence of SARS-COV-2 RNA on the particulate matter of Bergamo, which is not far from Milan and represents the epicenter of the Italian epidemic, seems to confirm (at least in case of atmospheric stability and high PM concentrations, as it usually occurs in Northern Italy) that the virus can create clusters with the particles and be carried and detected on PM10. Although no assumptions can be made concerning the link between this first experimental finding and COVID-19 outbreak progression or severity, the presence of SARS-COV-2 RNA on PM10 of outdoor air samples in any city of the world could represent a potential early indicator of COVID-19 diffusion. Searching for the viral genome on particulate matter could therefore be explored among the possible strategies for adopting all the necessary preventive measures before future epidemics start.

Air Pollution and Estimated Health Costs Related to Road Transportations of Goods in Italy: A First Healthcare Burden Assessment.

Background: The Italian Society of Environmental Medicine has performed a preliminary assessment of the health impact attributable to road freight traffic in Italy. Methods: We estimated fine particulate matter (PM10, PM2.5) and nitrogen oxides (NOx) generated by road transportation of goods in Italy considering the number of trucks, the emission factors and the average annual distance covered in the year 2016. Simulations on data concerning Years of Life Lost (YLL) attributable to PM2.5 (593,700) and nitrogen oxides NO2 (200,700) provided by the European Environmental Agency (EEA) were used as a proxy of healthcare burden. We set three different healthcare burden scenarios, varying from 1/5 to 1/10 of the proportion of the overall particulate matter attributable to road freight traffic in Italy (about 7% on a total of 2262 tons/year). Results: Road freight traffic in Italy produced about 189 tons of PM10, 147 tons of PM2.5 and 4125 tons of NOx in year 2016, resulting in annual healthcare costs varying from 400 million up to 1.2 billion EUR per year. Conclusion: Road freight traffic has a relevant impact on air pollution and healthcare costs, especially if considered over a 10-year period. Any solution able to significantly reduce the road transportation of goods could decrease avoidable mortality due to air pollution and related costs.