Virus inhibitor

Extracts from 152 plant species, representing 46 different families, were screened for effects on tobacco mosaic virus (TMV) replication in cucumber cotyledons. Twenty species have shown enough activity to warrant further study. Several members of the Caprifoliaceae family increased virus replication. An extract of Lonicera involucrata enlarged the virus lesions in local lesion hosts and produced a thirty fold increase in virus titer, but had no effect on virus replication in systemic hosts. The active material appears to affect the virus defense mechanism of local lesion hosts. An extract of common geranium is an active virus inhibitor. It inactivates TMV and TMV-RNA (ribonucleic acid) in vitro by forming non-infectious complexes. In vivo, it also inhibited starch lesion formation in cucumber cotyledons incited by TMV infection. 

In our screening program for virus inhibitors and stimulators we used cucumber as an assay host, in which starch lesions are formed in proportion to the concentration of virus in the inoculum. 

In both cases, a seeming virus stimulator (twinberry extract) and a virus inhibitor (tannic acid) operated in a more or less similar way in the cucumber-TMV system. They both affect the host defense mechanism against virus infection. The active component in twin-berry extract exhibits a mild and temporary interference, thus permitting virus to make further rounds of gain (ringlike patterns) while tannic acid produces a strong and permanent interference. 

The influenza virus inhibitors, zanamivir, and oseltamivir, act outside the cell after virus particles have been formed. The dtugs have been designed to fit into the active site of the viral envelope enzyme neuraminidase, which is required to cleave sialic acid off the surface of the producing cells. When its activity is blocked, new virus particles stay attached to the cell surface through binding of the virus protein hemagglutinin to sialic acid and are prevented from spreading to other cells. 

Blunting the Swiss Army Knife of Hepatitis C Virus Inhibitors of NS3/4A Protease ... 

Scheme 6.123 Synthesis of the respiratory syncytial virus inhibitor RFI-641.

There are reports that plant virus inhibitors occur naturally in plants, and they could be proteins, glycoprote -ins, polysaccharides, phenols etc(7 5). Extracts of mosses, especially Sphagnum(76), algae(77) and Cassia of the family Leguminosae(7S) are effective in inhibiting tobacco mosaic virus(TMV), but much more work is needed to develop virici-des that may be sprayed safely and economically on crop plants in the field. 

A number of 2-alkyl-1,2,3-benzotriazinium salts similar to those described earlier have b n used in protective coatings and in the formulation of adhesives. 3-Alkyl-l,2,3-benzotriazin-4(3fl)-ones have been examined as potential irreversible inhibitors of chymotrypsin, and the 3-(l-adamantyl) derivative as a potential virus inhibitor. Some unspecified 1,2,3-benzotriazine derivatives have been tested as radioprotectant compounds (to complement the well-known mercap-toethylamine and mercaptoalkylisothiouronium compounds), but were found to be ineffective. ... 

Currently, two classes of drugs are available with antiviral activity against influenza viruses inhibitors of the ion channel activity of the M2 membrane protein, amantadine and rimantadine, and the neuraminidase inhibitors oseltamivir, and zanamivir. H5N1 viruses isolated from poultry and humans in Thailand and Viet Nam in 2004 invariably showed an amantadine-resistance indicating that amantadine treatment is not an option during the ongoing outb-treak in South-East Asia. 

NT527 Grasso, S. and R. J. Shepherd. Isolation and partial characterization of virus inhibitors from plant species taxonomically related to Phytolacca. Phytopathology 1978 68 199. 

Lam et al. (1994) have also used this trick of both mimicking and displacing the water molecule. They designed a series of 7-membered ring cyclic ureas, including 68, which is a potent enzyme = 0.27 nM) and virus inhibitor, and also has significant oral bioavailability. This compound is currently under clinical investigation. Crystal structures of 10 of these cyclic urea complexes with protease have been determined, and show that, as the... 

R. W. Sidwell and D. F. Smee, In vitro and in vivo assay systems for study of influenza virus inhibitors, Antiviral. Res., 48 (2000) 1-16. 

Virus inhibitor, 140. See also Antiviral agent Vulcanization accelerators, 438,440,441 2-thiazolyl disulfides, relation with mass spectral fragmentation, 412... 

Wheelock, E. F. (1965). Interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutinin. Science 149, 310-311. 

Ding W, Mitsner B, Krishnamurthy G et al (1998) Novel and specific respiratory syncytial virus inhibitors that target virus fusion. J Med Chem 41 2671-2675... 

Huntley CC, Weiss WJ, Gazumyan A et al (2002) RFI-641, a potent respiratory syncytial virus inhibitor. Antimicrob Agents Chemother 46 841-847... 

Yu K-L, Zhang Y, Civiello RL et al (2003) Fundamental structure-activity relationships associated with a new structural class of respiratory syncytial virus inhibitor. Bioorg Med Chem Lett 13 2141-2144... 

Cianci C, Genovesi EV, Lamb L et al (2004) Oral efficacy of a respiratory syncytial virus inhibitor in rodent models of infection. Antimicrob Agents Chemother 48 2448-2454... 

Dischino DD, Cianci CW, Civiello R et al (2003) Development of a photoaffinity label for respiratory syncytial virus inhibitors. J Label Compd Radiopharm 46 1105-1116... 

A substantial number of phosphonates have been prepared and tested against viral infections, including AIDS. Even relatively simple compounds such as the above-mentioned phosphonoformic acid (19, = 0) and phosphonoacetic acid (19, n= 1) were reported as antivirals and herpes virus inhibitors active against acyclovirresistant herpes and cytomegalovirus retinitis in patients with AIDS . The veterinary use has been mentioned ... 

Yu XM, Sainz B, Petukhov PA, Uprichard SL. Identification of hepatitis C virus inhibitors targeting different aspects of infection using a cell-based assay. Antimicrob Agents Chemother 2013 56(12) 6109-20. 

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