In vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity

Kawauchi²,

Nakai³

et al. 2001

Antivir Chem Chemother

Concanamycins A (Conmy A) and B (Conmy B), well-known inhibitors of the vacuolar proton-ATPase, were isolated from the culture broth of Streptomyces sp. strain FK51 as antiherpetic agents. These compounds showed potent inhibition of herpes simplex virus type 1 (HSV-1) replication in an in vitro assay system, having antiviral activities with 50% inhibitory concentrations of 0.072 and 0.51 ng/ml for Conmy A and Conmy B, respectively. While the attachment of HSV-1 to Vero cells was not inhibited, both of the compounds blocked the penetration of virus into host cells. When added to the late stages of virus replication, the concanamycins also exerted marked inhibitory effects on the production of viruses. Release of progeny viruses was found to be suppressed by the agents. SDS-PAGE analysis of isotope-labelled HSV-specific proteins revealed that the synthesis of β proteins was moderately inhibited and some of the glycoproteins were synthesized with reduced molecular weights. Western blot analysis using antibodies against two HSV-specific glycoproteins (gC and gD) showed differences in their syntheses between untreated and Conmy A-treated cells. Syncytium formation by HSV-1 strain HF was inhibited, and small plaques with rounded cells were formed in Conmy A-treated cell cultures. When wild-type HSV-1 was serially propagated under the selective pressure of Conmy A, and the resulting progeny viruses were grown in drug-free medium, their plaque morphology of syncytium and sensitivity to Conmy A were the same as those of parent virus. From these findings, antiherpetic activities of Conmy A and B might be mainly dependent on their activities as vacuolar proton-ATPase inhibitors with intracellular translocation of glycoproteins and the inhibition of the maturation of virus glycoproteins.

Section: Inhibition Of Virus Adsorptionmentioning

confidence: 99%

Characterization of Inhibitory Action of Concanamycins against Herpes Simplex Virus

Kawauchi²,

Nakai³

et al. 2001

Antivir Chem Chemother

“…8) Briefly, Vero cell suspension (4ϫ10 6 cell/ml), HSV-1 at 1 PFU per cell, and different concentrations of nostoflan or dextran sulfate were precooled at 4°C for 3 h before mixing. The mixtures were incubated at 4°C for 1 h to allow the virus binding to cells and to prevent the virus from penetrating into cells.…”

Section: Methodsmentioning

confidence: 99%

Anti-herpes Simplex Virus Target of an Acidic Polysaccharide, Nostoflan, from the Edible Blue-Green Alga Nostoc flagelliforme

Kanekiyo

Biological & Pharmaceutical Bulletin

Takenaka

et al. 2007

112

The acidic polysaccharide nostoflan was previously isolated as an antiviral component from the terrestrial alga Nostoc flagelliforme. In the present study, we examined the target for its anti-herpes simplex virus type 1 action. In time-of-addition experiments, the most sensitive stage of viral replication to nostoflan was found to be early events, including the virus binding and/or penetration processes. In order to determine what extent nostoflan may be involved in these processes, virus binding and penetration assays were separately performed. The results indicated that the inhibition of virus binding to but not penetration into host cells was responsible for the antiherpetic effect induced by nostoflan. Our study suggests that nostoflan may be a potential antiherpes agent.

“…Thus, the inhibitory effects of arctigenin on virus adsorption and penetration were examined according to the reported methods. 17,18) The compound did not interfere with virus attachment to host cells at the concentrations of 5, 25 and 50 mM (data not shown). The compound showed weak effects against the virus penetration in a concentration-dependent manner (Table 3).…”

Section: Effect Of Arctigenin On Virus Adsorption and Penetrationmentioning

confidence: 99%

Therapeutic Effect of Arctiin and Arctigenin in Immunocompetent and Immunocompromised Mice Infected with Influenza A Virus

Biological & Pharmaceutical Bulletin

Narutaki

Nagaoka

et al. 2010

142

Arctiin and its aglucone, arctigenin from the fruits of Arctium lappa L. showed potent in vitro antiviral activities against influenza A virus (A/NWS/33, H1N1) (IFV). Based on the data from time-of-addition experiments and on release tests of progeny viruses, arctigenin was assumed to interfere with early event(s) of viral replication after viral penetration into cells, and to suppress the release of progeny viruses from the host cells. Arctiin was orally effective against either IFV-inoculated normal or 5-fluorouracil (5-FU)-treated mice, being less effective as compared with oseltamivir. Noticeably, arctiin produced a larger amount of virus-specific antibody than those of control and oseltamivir in sera collected from 5-FU-treated mice. Furthermore, oral treatment of 5-FU-treated mice with arctiin did not induce any resistant viruses, although the same treatment with oseltamivir induced resistant viruses at a 50% frequency. When the combination of arctiin and oseltamivir was administered to normal mice infected with IFV, the virus yields in both bronchoalveolar lavage fluids and lungs were significantly reduced relative to those in the mice treated with arctiin or oseltamivir alone. Thus, monotherapy of arctiin or combined therapy of arctiin with oseltamivir would be another treatment option for influenza.