T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC50s) of 0.013 to 0.48 μg/ml, while it showed no cytotoxicity at concentrations up to 1,000 μg/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitor-resistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC50s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 × 102 PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.

In Vitro and In Vivo Activities of Anti-Influenza Virus Compound T-705

Antiviral Natural Products and Herbal Medicines

The methanol extract from the whole plant of Geum japonicum was found to inhibit the human immunodeficiency virus (HIV-1) protease. Through bioassay-directed fractionation of the extract, a new triterpene acid along with five known triterpene acids, ursolic acid, epipomolic acid, maslinic acid, euscaphic acid, and tormentic acid, were isolated. The structure of the new compound was determined by spectral means including 1H-1H COSY, HMQC, HMBC, and NOE experiments to be 2 alpha, 19 alpha-dihydroxy-3-oxo-12-ursen-28-oic acid (1). Of these compounds, 1, ursolic acid, and maslinic acid showed potent inhibitory activity against HIV-1 protease.

Anti-HIV triterpene acids from Geum japonicum

A bioactivity-guided fractionation of an extract of Terminalia bellerica fruit rind led to the isolation of two new lignans named termilignan (1) and thannilignan (2), together with 7-hydroxy-3',4'-(methylenedioxy)flavan (3) and anolignan B (4). All four compounds possessed demonstrable anti-HIV-1, antimalarial, and antifungal activity in vitro.

New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica.

Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo.

Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice

Antiviral agent containing crude drug.

Hot aqueous and methanol extracts of the rhizomes of Woodwardia orientalis were tested for their in vitro antiviral activity against herpes simplex virus type 1 (HSV-1), poliovirus type 1, and measles virus by plaque reduction assay. The aqueous extract of W. orientalis reduced the plaque forming ability of HSV-1 and poliovirus more strongly than did the methanol extract. By bioassay-directed fractionation of the aqueous extract, a new glucoside, woodorien (1), along with five known compounds were isolated from an EtO Ac-soluble fraction that had antiviral activity. The structures of these compounds were determined by the use of two dimensional (2D) NMR techniques (1H-1H correlation spectroscopy (COSY), 1H-13C COSY and heteronuclear multiple-bond multiple-quantum coherence (HMBC)). Woodorien (1) was the most potent inhibitor against HSV-1 among the isolated compounds.

Isolation and structure of woodorien, a new glucoside having antiviral activity, from Woodwardia orientalis

A new hydrolyzable tannin, geponin, in addition to six known compounds were isolated from the aqueous extract of whole plant of Geum japonicum and their structures were determined by the use of 2D nmr. Geponin and gallic aldehyde showed potent antiviral activity against HSV-1 among the isolated seven compounds. These may contribute antiviral activity of the aqueous extract of G. japonicum

A new hydrolyzable tannin from Geum japonicum and its antiviral activity

PURPOSE:To provide an antiviral agent containing galenical drugs. CONSTITUTION:This invented a antiviral agent characteristically contains one or more kinds of galenical drugs selected from Ainsliaea fragrans Champ, Alpinia officinarum Hance, Andropogon zizaniodes (L.) Urban, Areca catechu L., Artemisia princeps Pamp., Belamcanda chinensis (L.) DC., Brainia insignis (Hook.) J. Sm., Brucea javanica (L.) Merr, Caesalpinia sappan L., Cassia fistula L., Chamaesyce hyssopifolia Small, Cinnamomum cassia Blume, Cinnamomum sintok Blume, Cytromium fortunei J. Sm., Drynaria fortunei (Kunze) J. Smith, Dryopteris crassirhizoma Nakai, Elaeocarpus grandiflorus Smith, Elephantopus scaber L., Erythroxylum lucidum H. Baill., Geranium thunbergii Sieb. et Zucc., Hamelia axillaris Swartz, Jatropha curcas L., Loranthus parasiticus (L.) Merr., Matteuccia struthiopteris (L.) Todaro, Mylabris sidae Fabr., Panax ginseng C.A. Meyer, Parameria laevigata Moldenke, Perilla frutescens Britton var. acuta Kudo, Physalis angulata L., Plagiogyria matsumureana Makino, Quercus salicina Blume, Sarcandra glabra (Thunb.) Nakai, Serjania mexicana Seem., Sophora japonica L., Sophora subprostrata Chun et T. Chen, Strychnos nux-vomica L., Syzygium aromaticum (L.) Merr. et Perry, Terminalia arjuna Wight et Arn., Terminalia belerica Roxb., Usnea misaminensis Vain., Waltheria indica L. Woodfordia floribunda Salisb., Woodwardia orientalis Sw., Zanthoxylum bungeanum Maxim., Zizyphus jujuba Miller var. inermis Rehder.

Takao Matsumoto

Papers

Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice

Antiviral agent containing crude drug.

Isolation and structure of woodorien, a new glucoside having antiviral activity, from Woodwardia orientalis

A new hydrolyzable tannin from Geum japonicum and its antiviral activity

Galenical drug-containing antiviral agent