Evaluation of (1R,2R)-1-(5 '-methylfur-3 '-yl)propane-1,2,3-triol, a sphydrofuran derivative isolated from a Streptomyces species, as an anti-herpesvirus drug

(1R,2R)-1-(5'-Methylfur-3'-yl)propane-1,2,3-triol (MFPT), a stable anhydro derivative of sphydrofuran, was obtained from the culture broth of Streptom yces sp. strain FV60 as an inhibitor of herpes simplex virus type 1 (HSV-1) . The compound showed antiherpetic activity with a 50% Inhibitory concentra tion of 1.2 mu M in an in vitro assay system. Although the binding of virus to host cells was not Inhibited, the penetration of virus into cells was m oderately blocked by MFPT. Some of the viruses, once they had penetrated ce lls, failed to form plaques in the presence of MFPT. When added to the late stages of HSV-1 replication, MFPT also inhibited virus production. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis of isotope-lab elled HSV-specific proteins revealed that a protein or proteins with reduce d molecular weight (about 120 kDa) was clearly detected in cells treated wi th MFPT. Western blot analysis with antibodies against three HSV-specific g lycoproteins (gB, gC and gD) showed a significant difference in gC synthesi s between untreated and MFPT-treated cells. Release of progeny viruses was suppressed by MFPT. Syncytium formation by HSV-1 strain HF was inhibited an d small plaques with rounded cells were formed in MFPT-treated cell culture s. When wild-type HSV-1 was serially propagated under the selective pressur e of MFPT, resistant virus emerged. MFPT-resistant progeny were accompanied by the formation of plaques with rounded cells. These results, taken toget her, suggest that MFPT might act by limiting the maturation of HSV-specific glycoproteins, particularly of HSV-1 gC.