My search for a selective antiviral chemotherapy started more than 40 years ago with interferon inducers, then shifted to nucleoside analogs with the discovery of BVDU (brivudin), a highly selective anti-HSV-1 and anti-VZV agent, and to dideoxynucleoside analogs such as d4T (stavudine), anti-HIV agents. The search culminated in the discovery of acyclic nucleoside phosphonates (ANPs) (in collaboration with Antonin Holý), a key class of compounds active against HIV, hepatitis B virus, and DNA viruses at large; the best known of these compounds is tenofovir. Along the way, the principle of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was established. This work, initiated in collaboration with the late Paul A.J. Janssen, eventually led to the identification of rilpivirine as perhaps an "ideal" NNRTI.
The double‐helical RNA interferon inducer, poly(inosinic acid) · poly(cytidylic acid) [(I) n · (C) n ], is rapidly degraded by nucleases present in human plasma (serum). When incubated at 37°C with 50% human plasma, (I) n · (C) n (10 μg/ml) showed a half‐life of 6 min, [as assessed by residual acid insoluble radioactivity of an (I) n · (C) n preparation which was 3 H‐labelled in the (C) n component]. Sucrose velocity analysis revealed that human plasma nucleases specifically hydrolyzed the (C) n strand of (I) n · (C) n , as assessed with (I) n · (C) n preparations that were 3 H‐labelled in either (I) n or (C) n . The plasma nucleases that were responsible for the degradation of (I) n · (C) n resembled pancreatic ribonuclease A rather than T 1 ribonuclease in substrate specificity. (I) n · (C) n became completely inactive as an inerferon inducer when it was incubated with 50% human plasma or serum. However, its interferon‐inducing capacity was fully restored if (C) n but not (I) n was added to the host cells, after these had been exposed to the inactivated (I) n · (C) n . That the inactivating effect of human plasma on the interferon‐inducing potency of (I) n · (C) n could solely be attributed to hydrolysis of the (C) n strand was further supported by the finding that two analogues of (I) n · (C) n , which had become more resistant to degradation by pancreatic ribonuclease by virtue of some substitutions in the (C) n strand, i.e. a bromine at C‐5, (I) n · (br 5 C) n , or a sulfur at C‐2, (I) n · (s 2 C) n , were not inactivated in the presence of 50% human plasma (or serum).
A dedicated SLS material (i.e. LaserForm) has given better wear resistance than SLM stainless steel and tool steel. It shows that preferring SLM over SLS for Rapid Tooling is not necessarily the best choice.
