The use of natural compounds and, in general, the use of Complementary and Alternative Medicine (CAM), is growing steadily worldwide, both due to commercial pressure and the increasing use of self-medication and the desire to manage one\'s own personal health and well-being. Patients facing a cancer diagnosis are also strongly pressured to use these compounds, which are often added to standard therapeutic regimens, that should instead be based solely on diagnostic and therapeutic care pathways (DTCP) or evidence-based medicine (EBM). This study presents two clinical cases of cancer patients who presented to the pharmaceutical consultation service (PCD-Pharmacy Clinical Desk) established at the CRO Institute in Aviano, Italy. Both patients were using natural products along with prescribed chemotherapy. In the first case, a 55-year-old woman diagnosed with bilateral breast cancer with bone metastases, who was using natural compounds based on diosmin, escin (or aescin) and resveratrol in combination with ribociclib anticancer therapy, a severe ADR (neutropenia) was identified as a consequence of the drug-natural product interaction. In the second case, following a detailed medication review by the PCD, we avoided taking a therapeutic treatment (with natural compounds) that in itself could potentially render chemotherapy ineffective in a 57-year-old woman with multiple infiltrating ductal carcinoma of the left breast; the patient was planning to take a natural product containing St. John\'s Wort tincture and lemon balm tincture, in combination with paclitaxel and trastuzumab. In addition, we describe the corrective actions taken, thus outlining the main objectives of the activity of the PCD\'s pharmacy counseling service: first, to identify, report, and manage adverse drug reactions (ADRs), and second, to identify therapeutic combinations that present potential risks of toxicity or ineffectiveness of the drug therapy itself.

The rational search for allosteric modulators and the allosteric mechanisms of these modulators in the presence of mutations is a relatively unexplored field. Here, we established novel in silico approaches and applied them to SARS-CoV-2 main protease (Mpro) as a case study. First, we identified six potential allosteric modulators. Then, we focused on understanding the allosteric effects of these modulators on each of its protomers. We introduced a new combinatorial approach and dynamic residue network (DRN) analysis algorithms to examine patterns of change and conservation of critical nodes, according to five independent criteria of network centrality. We observed highly conserved network hubs for each averaged DRN metric on the basis of their existence in both protomers in the absence and presence of all ligands (persistent hubs). We also detected ligand specific signal changes. Using eigencentrality (EC) persistent hubs and ligand introduced hubs we identified a residue communication path connecting the allosteric binding site to the catalytic site. Finally, we examined the effects of the mutations on the behavior of the protein in the presence of selected potential allosteric modulators and investigated the ligand stability. One crucial outcome was to show that EC centrality hubs form an allosteric communication path between the allosteric ligand binding site to the active site going through the interface residues of domains I and II; and this path was either weakened or lost in the presence of some of the mutations. Overall, the results revealed crucial aspects that need to be considered in rational computational drug discovery.