The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (M pro ) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent M pro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 M pro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

The uncontrolled spread of the COVID-19 pandemic caused by the new coronavirus SARS-CoV-2 during 2020–2021 is one of the most devastating events in the history, with remarkable impacts on the health, economic systems, and habits of the entire world population. While some effective vaccines are nowadays approved and extensively administered, the long-term efficacy and safety of this line of intervention is constantly under debate as coronaviruses rapidly mutate and several SARS-CoV-2 variants have been already identified worldwide. Then, the WHO’s main recommendations to prevent severe clinical complications by COVID-19 are still essentially based on social distancing and limitation of human interactions, therefore the identification of new target-based drugs became a priority. Several strategies have been proposed to counteract such viral infection, including the repurposing of FDA already approved for the treatment of HIV, HCV, and EBOLA, inter alia. Among the evaluated compounds, inhibitors of the main protease of the coronavirus (Mpro) are becoming more and more promising candidates. Mpro holds a pivotal role during the onset of the infection and its function is intimately related with the beginning of viral replication. The interruption of its catalytic activity could represent a relevant strategy for the development of anti-coronavirus drugs. SARS-CoV-2 Mpro is a peculiar cysteine protease of the coronavirus family, responsible for the replication and infectivity of the parasite. This review offers a detailed analysis of the repurposed drugs and the newly synthesized molecules developed to date for the treatment of COVID-19 which share the common feature of targeting SARS-CoV-2 Mpro, as well as a brief overview of the main enzymatic and cell-based assays to efficaciously screen such compounds.

The study of oxygen heterocyclic compounds (coumarins, psoralens, polymethoxylated flavones) in natural matrices such as citrus oils is not easy due to the difficulty of obtaining standards at the required level of purity and the diversity of structures present in each kind of sample. In this work, standards were either isolated by preparative LC methods from citrus oils or synthesized, then characterized by their physicochemical parameters and spectroscopic techniques, and further used for qualitative and quantitative calculations in citrus essential oils and products made with them (Earl Grey tea, liquors, juices). An HPLC method using an innovative partially porous particle HPLC column enabled baseline separation of all analytes. The method developed was validated in terms of detection limit, quantitation limit, linearity, and precision as repeatability and intralaboratory reproducibility.

Phosphonated carbocyclic 2′-oxa-3′-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2′-oxa-3′-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.

New bioactive epimeric derivatives of oleuropein have been detected in olive fruits and structurally characterized by (1)H and (13)C NMR. These hydrolytic metabolites, obtained by enzymatic catalysis, can be molecular microcomponents, present in Mediterranean food, table olives, and olive oil, responsible for complex sensorial attributes and for pathogen natural defense.

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The oleuropein hydrolytic conversion, under biomimetic conditions, induced by the endogenous enzymatic system of the olive fruit, has been monitored by the intermediate derivative formation through (1)H and (13)C NMR spectra; the assigned molecular structures reveal the identity of new bioactive biophenolic metabolites, the hemiacetal aglycon, and the two epimeric dialdehydes, which influence the pathogen antagonism of olive fruits and the hedonistic-sensorial characteristics of olive oil.

Enantiomers of 4'-aza-2',3'-dideoxynucleosides have been prepared by two different synthetic approaches, on the basis of 1,3-dipolar cycloaddition of a chiral nitrone. Cytotoxicity and apoptotic activity have been investigated. (5'S)-5-Fluoro-1-isoxazolidin-5-yl-1H-pyrimidine-2,4-dione [(-)-AdFU], while showing low level of cytotoxicity, is a good inductor of apoptosis on lymphoid and monocytoid cells, acting as a strong potentiator of Fas-induced cell death.