The ten stories told here deal with (i) ribavirin as an inhibitor of IMP dehydrogenase and (ii) ribavirin, in combination with pegylated interferon, as the present "standard of care" for hepatitis C; (iii) S-adenosylhomocysteine hydrolase inhibitors as antiviral agents; (iv) new adamantadine derivatives for the treatment of influenza A virus infections; (v) 5-substituted 2'-deoxyuridines (i.e. IDU, TFT) for the treatment of herpes simplex virus (HSV) infections; (vi) acyclic guanosine analogues (e.g. acyclovir) for the treatment of HSV infections; (vii) OMP decarboxylase inhibitors (i.e. pyrazofurin) and CTP synthetase inhibitors (i.e. cyclopentenylcytosine) as possible antiviral agents; (viii) the future of cidofovir (and alkoxyalkyl esters thereof) and ST-246 as potential antipoxvirus agents; (ix) the two decade journey from tivirapine to rilpivirine in the ultimate therapy of HIV infections; and (x) the extension of the therapeutic application of tenofovir disoproxil fumarate (Viread) to the treatment of hepatitis B virus infection, in addition to HIV infection.
Twenty-five patients with haematological diseases were treated orally with the highly potent and selective anti-herpes agent, bromovinyldeoxyuridine (BVDU), in a dosage of 7.5 mg/kg/day (divided over three or four doses a day) for 5 days for an intercurrent mucocutaneous herpesvirus infection. Of these 25 patients, 8 were severely granulocytopenic at the time of the viral infection, and 12 recently had undergone bone-marrow transplantation; 5 were under cytotoxic therapy for a lymphoproliferative disorder; 13 had herpes simplex virus type 1 (HSV-1); 1 had herpes simplex virus type 2 (HSV-2); and 11 had varicella-zoster virus (VZV) infection. In all but two patients, BVDU arrested progression of the HSV or VZV infection within 1-2 days after treatment was started. One of the two patients who failed to respond to BVDU had an HSV-2 infection. The other had an HSV-1 infection, which was highly sensitive to BVDU in vitro; BVDU may have failed in this patient because of incomplete drug intake or profuse diarrhoea, or both. The results of this preliminary uncontrolled clinical trial suggest that BVDU may be an effective and safe drug for the oral treatment of HSV-1 and VZV infections in severely immunosuppressed patients.
The determination of the phase shift and the light shift in our optically pumped Cs beam is reported here. We show that an error on the phase difference value determined by our fit method, without beam reversal, can be induced if the light shift is not taken into account. If the experimental data are corrected for the light shift, the results of the fit method are in very good agreement with the beam reversal results. This allows us to reduce the related uncertainty in the accuracy budget of our standard. The resulting overall accuracy of the standard is now estimated to be 6.3x10(-15).
HIV infection has been a greater challenge to current medicine than any other viral disease ofmodem times. HIV leads to a persistent infection and the virus has an immense genetic flexibility under se
Synthesis and biological evaluation of a carbocyclic azanoraristeromycin siderophore conjugate 22 is reported. Coupling of previously prepared L-alanyl-4'-azanoraristeromycin 19 with protected tripeptide trihydroxamate 20, followed by hydrogenolytic removal of all protecting groups, provided the first carbocylic azanoraristeromycin siderophore conjugate (22, 8 with iron). Compounds 19 and 22 showed inhibitory activity against tumor cells, and conjugate 22, in particular, displayed significant activity against those viruses (i.e. reo, parainfluenza, vaccinia, cytomegalo) that are known to be inhibited by S-adenosylhomocysteine hydrolase inhibitors.
Although the presence of free 2'-hydroxyl groups in both strands of a double-stranded RNA complex has been recognized as one of the major requisites for the interferon inducing activity of double-stranded RNAs, we have found a particular analog of (I)n·(C)n, in which the 2'-hydroxyls of the purine strand were replaced by azido groups [(dIz)n·(C)n], to be exquisitely effective in inducing interferon. Various other 2'-azido analogs, i.e. (dIz)n·(brC)n, (I)n·(dCz)n, (dAz)n·(U)n, (dAz)n·(rT)n and (dAz)n·(dUz)n were inactive as inducers of interferon. Thus we come to the conclusion that the interferon inducing system recognizes total threedimensional conformation of the double-stranded RNA.
