Glycyrrhizin (GL) was shown to inhibit SARS-coronavirus (SARS-CoV) replication in vitro. Here the anti-SARS-CoV activity of 15 GL derivatives was tested. The introduction of 2-acetamido-beta-d-glucopyranosylamine into the glycoside chain of GL resulted in 10-fold increased anti-SARS-CoV activity compared to GL. Amides of GL and conjugates of GL with two amino acid residues and a free 30-COOH function presented up to 70-fold increased activity against SARS-CoV but also increased cytotoxicity resulting in decreased selectivity index.

Although human cytomegalovirus (HCMV) is generally not regarded to be an oncogenic virus, HCMV infection has been implicated in malignant diseases from different cancer entities. On the basis of our experimental findings, we developed the concept of "oncomodulation" to better explain the role of HCMV in cancer. Oncomodulation means that HCMV infects tumor cells and increases their malignancy. By this concept, HCMV was proposed to be a therapeutic target in a fraction of cancer patients. However, the clinical relevance of HCMV-induced oncomodulation remains to be clarified. One central question that has to be definitively answered is if HCMV establishes persistent virus replication in tumor cells or not. In our eyes, recent clinical findings from different groups in glioblastoma patients and especially the detection of a correlation between the numbers of HCMV-infected glioblastoma cells and tumor stage (malignancy) strongly increase the evidence that HCMV may exert oncomodulatory effects. Here, we summarize the currently available knowledge about the molecular mechanisms that may contribute to oncomodulation by HCMV as well as the clinical findings that suggest that a fraction of tumors from different entities is indeed infected with HCMV.

Six p53 wild-type cancer cell lines from infrequently p53-mutated entities (neuroblastoma, rhabdomyosarcoma, and melanoma) were continuously exposed to increasing concentrations of the murine double minute 2 inhibitor nutlin-3, resulting in the emergence of nutlin-3-resistant, p53-mutated sublines displaying a multi-drug resistance phenotype. Only 2 out of 28 sublines adapted to various cytotoxic drugs harboured p53 mutations. Nutlin-3-adapted UKF-NB-3 cells (UKF-NB-3rNutlin10 μM, harbouring a G245C mutation) were also radiation resistant. Analysis of UKF-NB-3 and UKF-NB-3rNutlin10 μM cells by RNA interference experiments and lentiviral transduction of wild-type p53 into p53-mutated UKF-NB-3rNutlin10 μM cells revealed that the loss of p53 function contributes to the multi-drug resistance of UKF-NB-3rNutlin10 μM cells. Bioinformatics PANTHER pathway analysis based on microarray measurements of mRNA abundance indicated a substantial overlap in the signalling pathways differentially regulated between UKF-NB-3rNutlin10 μM and UKF-NB-3 and between UKF-NB-3 and its cisplatin-, doxorubicin-, or vincristine-resistant sublines. Repeated nutlin-3 adaptation of neuroblastoma cells resulted in sublines harbouring various p53 mutations with high frequency. A p53 wild-type single cell-derived UKF-NB-3 clone was adapted to nutlin-3 in independent experiments. Eight out of ten resulting sublines were p53-mutated harbouring six different p53 mutations. This indicates that nutlin-3 induces de novo p53 mutations not initially present in the original cell population. Therefore, nutlin-3-treated cancer patients should be carefully monitored for the emergence of p53-mutated, multi-drug-resistant cells.

Initial in vitro investigations demonstrated type I interferons (IFNs: IFN-alpha, IFN-beta) to inhibit replication of SARS coronavirus (SARS-CoV), but found the nucleoside analogue ribavirin ineffective in Vero cells. In this report, ribavirin was shown to inhibit SARS-CoV replication in five different cell types of animal or human origin at therapeutically achievable concentrations. Since clinical anti-SARS-CoV activity of type I interferons or ribavirin is limited, we investigated the combination of IFN-beta and ribavirin. Determination of the virus yield indicated highly synergistic anti-SARS-CoV action of the combination suggesting the consideration of ribavirin plus IFN-beta for the treatment of SARS.