susceptibility of cyclin D1, but not of non-transgenic littermates, to pristane-induced lymphoma.We have also directly investigated a 'two-hit' model for lymphomagenesis. As mantle cells express bcl-2, and it seemed logical that a proliferation gene, bcl-1/cyclinD1, and an antiapoptotic gene, bcl-2, might have cooperative effects, we crossbred Em-cyclin D1 X Em-bcl2 mice. None of more than 50 double-transgenic mice developed lymphoma.As lymphoma susceptibility is strain-specific, we crossed the Em-cyclin D1 transgenic mice, which are in C57BL6 background, with wild-type BALB/c mice for nine generations and no spontaneous lymphomas occurred in the Em-cyclin D1/BALBc mice.The histology of this lymphoma model and its characterization as CD5 þ , CD23À, cyclin D1 þ monoclonal IgM þ B cells indicate that pristane injection of older Em-cyclin D1 transgenic mice recapitulates human MCL. Thus, we have developed a murine model of MCL that relies on at least three distinct stages of lymphomagenesis. The mice must have the initiating event of dysregulated cyclin D1 expression, here due to the Em-cyclin D1 transgene. They must then undergo changes associated with aging that may sensitize the cells to the effects of pristane. This indicates age dependence for developing lymphoma, reminiscent of the increased incidence of lymphoma in humans with aging. Finally, pristane injections are required for the ultimate progression to lymphoma. This may act as a nonspecific mitogenic stimulus that permits additional genetic alterations to occur in dividing B lymphocytes or as an immune stimulant leading to cytokine release (as with IL-6 for plasmacytomas).Significant differences are evident between this lymphoma and the plasmacytoma model. 3 First, C57BL6 mice are resistant to plasmacytoma development. Previous studies have shown that a peritoneal inflammatory response with granuloma formation does occur in these mice, however. Second, pristane-induced plasmacytomas secrete IgA, whereas the lymphomas in our model express RNA for Cm and surface IgM. Third, pristane-induced plasmacytomas occur when young mice are injected and have a latency of about 1 year, whereas the lymphoma in our model occurs only when older mice are injected and then has a short latency period.

Respiratory Syncytial Virus (RSV) is the top cause of infant hospitalization globally, with no effective treatments available. Researchers have sought small molecules to target the RNA-dependent RNA Polymerase (RdRP) of RSV, which is essential for replication and transcription. Based on the cryo-EM structure of the RSV polymerase, in silico computational analysis including molecular docking and the protein-ligand simulation of a database, including 6554 molecules, is currently undergoing phases 1–4 of clinical trials and has resulted in the top ten repurposed compound candidates against the RSV polymerase, including Micafungin, Totrombopag, and Verubecestat. We performed the same procedure to evaluate 18 small molecules from previous studies and chose the top four compounds for comparison. Among the top identified repurposed compounds, Micafungin, an antifungal medication, showed significant inhibition and binding affinity improvements over current inhibitors such as ALS-8112 and Ribavirin. We also validated Micafungin’s inhibition of the RSV RdRP using an in vitro transcription assay. These findings contribute to RSV drug development and hold promise for broad-spectrum antivirals targeting the non-segmented negative-sense (NNS) RNA viral polymerases, including those of rabies (RABV) and Ebola (EBOV).