Bromovinyldeoxyuridine (BVdUrd) is a potent antiherpesvirus compound with low cytotoxicity. To gain an insight into its selectivity and mechanism of inhibition, we chemically synthesized the 5'-triphosphate of BVdUrd, BVdUTP, and (3, 4); in addition, a DNase (5) and a nucleoside phosphotransferase (6) are induced in cells upon infection with HSV. These virus-induced enzymes are significantly different from their cellular counterparts in many of their properties (7-9). For example, the HSV-induced DNA polymerase differs from the host cellular DNA polymerases a,

Nine triterpenes with antiviral activity against Herpes simplex virus types I and II in vitro were isolated from dammar resin. Each compound caused a significant reduction in viral cytopathic effect when Vero cells were exposed continuously to 1-10 micrograms/ml of compound for 48 h after viral challenge. The triterpenes were identified as dammaradienol [1], dammarenediol-II [2], hydroxydammarenone-I [3], ursonic acid [5], hydroxyhopanone [11], dammarenolic acid [15], shoreic acid [16], eichlerianic acid [17], and a novel compound, hydroxyoleanonic lactone [7], on the basis of their chromatographic, spectroscopic, and physical properties.

The inhibition of humanimmunodeficiency virus (HIV) reverse transcriptase by certain antibiotics and related compounds was studied in comparisonwith that of avian myeloblastosis virus (AMV)reverse transcriptase and cellular DNApolymerases a and £. In general, compoundsthat inhibited HIVreverse transcriptase also inhibited AMV reverse transcriptase. For example, 10^g/ml of the isoquinoline quinones used in this study inhibited approximately 80 % of the activity of reverse transcriptases of HIV and AMV,but did not inhibit the activity of DNApolymerases a and fi even at 50^g/ml. AMV enzymewas more sensitive than HIV enzyme to colistin, enduracidins A and B, janiemycin, glysperin A, and thielavins A and B. The streptonigrin alkyl esters, however, inhibited HIVreverse transcriptase only. Sakyomicin A, luzopeptins, ellagic acid and suramine inhibited the activities of reverse transcriptases and cellular DNApolymerases.Reverse transcription, a step catalyzed by the unique DNApolymerase, reverse transcriptase, is a pivotal step in the replication of retroviruses and in the stable inheritance of viral genome. An effective inhibitor of reverse transcriptase may selectively block viral replication and therefore, the enzyme has been one of the molecular targets in antiviral studies for manyyears. We have undertaken a search for inhibitors of avian myeloblastosis virus (AMV)reverse transcriptase among antibiotics and related compounds. Humanimmunodeficiency virus (HIV), a causative agent for acquired im- Materials and Methods MaterialsAMV reverse transcriptase was purchased from Seikagaku KogyoCo., Ltd. HIV reverse trans-

A poloxamer surfactant, CRL8131, was evaluated for activity against Mycobacterium tuberculosis (Erdman) by itself and in combination with antibiotics in broth culture, in a macrophage cell line assay, and in testing with mice. In the broth culture, CRL8131 suppressed the growth of M. tuberculosis and produced synergistic effects in combination with isoniazid, rifampin, and streptomycin. It also displayed synergy with isoniazid and rifampin against two drug-resistant isolates. In the macrophage cell line assay, CRL8131 produced a synergistic effect on intracellular killing of M. tuberculosis by isoniazid, rifampin, streptomycin, pyrazinamide, thiacetazone, D-cycloserine, ethionamide, amikacin, clindamycin, and p-aminosalicylic acid. It demonstrated no synergy or antagonism with ethambutol, gentamicin, kanamycin, ciprofloxacin, or nalidixic acid. Finally, with C57BL/6 mice infected with M. tuberculosis, a combination of CRL8131 and either thiacetazone or pyrazinamide produced 100% survival at 40 days whereas the antibiotics produced only 33% survival and CRL8131 produced 0% survival when used as single agents. This improved survival rate was associated with a significant reduction in the number of organisms in the lungs and spleens of infected mice.The feasibility of using large hydrophobic nonionic surfactants for treating mice infected with Mycobacterium tuberculosis was demonstrated over 40 years ago. Cornforth et al. reported that a single injection of Triton WR-1339 significantly prolonged the survival of mice infected intravenously with a large dose of M. tuberculosis organisms (6,8). The injection of a surfactant was effective if given either before or up to 5 days after infection. The surfactant suppressed growth of M. tuberculosis in macrophage cultures and in intact mice but was inactive in broth culture. It was found to localize in macrophages after systemic injection (20). This information led to the hypothesis that Triton WR-1339 and similar agents suppressed tuberculosis infection by modulating host-parasite interactions rather than by direct action on the organism. It was reported further that Triton WR-1339 produced a synergistic suppression of M. tuberculosis growth in mice when used in combination with rifampin and pyrazinamide (19). In spite of these promising findings, the development of surfactants as drugs was not pursued because of the discovery of more effective drugs and declining interest in the disease. However, the increasing incidence of disease in immunocompromised people and the emergence of multidrug-resistant strains of M. tuberculosis have renewed interest in novel antimycobacterial agents.We have investigated the biologic activities of poloxamers for over 10 years. Poloxamers are simple synthetic surfactants that consist of a central chain of hydrophobic polyoxypropylene (POP) flanked by two chains of hydrophilic polyoxyethylene (POE) (22). By varying the lengths of these chains, a homologous series of compounds which span nearly the entire spectrum of functional properties of no...

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