Antipicornavirus Drugs: Current Status

Diana, G.; Dc, Pevear

doi:10.1177/095632029700800502

Cited by 33 publications

(22 citation statements)

References 68 publications

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“…Aseptic meningitis may, particularly in children, be a common syndrome associated with EV; because of the difficulties in distinguishing viral from bacterial etiology and from other viral etiology, the detection of enteroviral RNA may eliminate unnecessary therapy [Chonmaitree et al, 1982;Rotbart 1991]. The possible treatment of EV infections with new antivirals open up a new need for detecting enteroviral RNA [Diana and Pevear, 1997], with particular application to agammaglobulinemic patients [Galama, 1997].…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, the most virulent forms of EVs infections can be fatal under several circumstances (i.e., status of immune system) and some persistent EV infection with meningoencephalitis can occur in agammaglobulinemic patients [McKinney et al, 1987]. Efficient antienteroviral chemotherapy has been recently described and results of clinical trials are available [Diana and Pevear, 1997] and may be attractive for treatment of agammaglobulinemic patients, in combination with gammaglobulins [Galama, 1997]. The involvement of lymphotropic HV, such as cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 (CMV, EBV, HHV6) as the cause of neurological syndromes is frequent among AIDS patients [Pedneault et al, 1992;Kondo et al, 1993;Rolfs, 1993;Luppi et al, 1994;Troendle-Atkins et al, 1994].…”

Section: Introductionmentioning

confidence: 99%

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Viral diagnosis of neurological infection by RT multiplex PCR: A search for entero- and herpesviruses in a prospective study

et al. 1999

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The diagnosis of a wide range of different neurological syndromes was established by a reverse transcription multiplex PCR assay. The presence of enterovirus and herpesviruses was studied in cerebrospinal fluid samples collected prospectively from 200 patients hospitalized with neurological diseases suspected of viral infection. Positive PCR results for enterovirus and neurotropic herpesvirus (herpes simplex, HSV, and varicella zoster, VZV) were obtained among the immunocompetent patients (55/156, 35%) who presented aseptic meningitis or encephalitis. Among immunocompromised patients the yield of positive PCR results was 41% (18/44), predominantly lymphotropic herpesviruses (15/44, 34%). Cytomegalovirus (CMV) DNA was detected in patients with several clinical syndromes, including encephalitis, chronic meningitis, retinitis, ventriculitis, polyradiculomyelitis, and myeloradiculitis. Epstein-Barr (EBV) and VZV-specific DNA sequences were detected in patients with either encephalitis, aseptic meningitis, and chronic meningitis. Dual infections of CMV and HSV or CMV and EBV were established in two AIDS patients with encephalitis and polyradiculomyelitis, respectively. The applications of this RT multiplex PCR assay are extensive and may prove to be particularly valuable for the rapid and sensitive diagnosis of neurological diseases in both immunocompetent and immunocompromised patients.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Viral diagnosis of neurological infection by RT multiplex PCR: A search for entero- and herpesviruses in a prospective study

et al. 1999

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“…Enviroxime {[2-amino-1-(isopropylsulfonyl)-6-benzimidazole phenyl ketone oxime]} is a rather broadspectrum picornavirus inhibitor that is thought to inhibit RNA replication by targeting the 3A protein-coding region of the viral RNA (10). Among the substances interacting with capsids, zinc is thought to bind to the surface canyon sites of rhinovirus to prevent attachment (15), although there is disputed evidence whether zinc-containing lozenges actually are therapeutic (11) (6). Some of these compounds are not very orally bioavailable (18), although pleconaril does have that capability.…”

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confidence: 99%

In Vitro Activity of Expanded-Spectrum Pyridazinyl Oxime Ethers Related to Pirodavir: Novel Capsid-Binding Inhibitors with Potent Antipicornavirus Activity

Barnard

Hubbard

Smee

et al. 2004

Antimicrob Agents Chemother

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Picornaviruses (PV) include human rhinovirus (HRV), the primary cause of the common cold, and the enteroviruses (EV), which cause serious diseases such as poliomyelitis, meningoencephalitis, and systemic neonatal disease. Although no compounds for PV infections have been approved in the United States, pirodavir was one of the most promising capsid-binding compounds to show efficacy in human clinical trials for chemoprophylaxis of the common cold. Susceptibility to hydrolysis precluded its use as an oral agent. We have developed orally bioavailable pyridazinyl oxime ethers that are as potent as pirodavir. Compounds BTA39 and BTA188 inhibited a total of 56 HRV laboratory strains and three clinical isolates as determined by neutral red uptake assay. At concentrations of <100 nM, BTA39 inhibited 69% of the HRV serotypes and isolates evaluated, BTA188 inhibited 75%, and pirodavir inhibited 59% of the serotypes and isolates. The 50% inhibitory concentrations (IC 50 s) for the two compounds ranged from 0.5 nM to 6,701 nM. The compounds also inhibited EV, including coxsackie A and B viruses (IC 50 ‫؍‬ 773 to 3,608 nM) and echoviruses (IC 50 ‫؍‬ 193 to 5,155 nM). BTA39 only inhibited poliovirus strain WM-1 at 204 nM, and BTA188 only inhibited poliovirus strain Chat at 82 nM. EV 71 was inhibited by BTA39 and BTA188, with IC 50 s of 1 and 82 nM, respectively. Both compounds were relatively nontoxic in actively growing cells (50% cytotoxic doses, >4,588 nM). These data suggest that these oxime ethers warrant further investigation as potential agents for treating selected PV infections.

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“…A similar approach has been used to identify a hydrophobic pocket in the viral capsid of rhinovirus which acts as a binding site for antiviral compounds which prevent uncoating of the virus after entry into cells (Rossmann, 1988(Rossmann, , 1989(Rossmann, , 1993. The WIN series of picornavirus inhibitors was developed using this technique (Badger et al, 1988) leading to the clinical evaluation of pleconaril for the treatment of picornavirus infections (Diana & Pevear, 1997).…”

Section: L1 and L2 Capsid Proteinsmentioning

confidence: 99%

Molecular Targets for Human Papillomaviruses: Prospects for Antiviral Therapy

Phelps

Barnes

Lobe

1998

Antivir Chem Chemother

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A substantial medical need exists for the development of antiviral medicines for the treatment of diseases associated with infection by human papillomaviruses (HPVs). HPVs are associated with various benign and malignant lesions including benign genital condyloma, common skin warts, laryngeal papillomas and anogenital cancer. Since treatment options are limited and typically not very satisfactory, the development of safe and effective antiviral drugs for HPV could have substantial clinical impact. In the last few years, exciting advances have been made in our understanding of papillomavirus replication and the effects that the virus has on growth of the host cell. Although still somewhat rudimentary, techniques have been developed for limited virion production in vitro offering the promise of more rapid advances in the dissection and understanding of the virus life cycle. Of the 8–10 HPV gene products that are made during infection, only one encodes enzymatic activities, the E1 helicase. Successful antiviral therapies have traditionally targeted viral enzymes such as polymerases, kinases and proteases. In contrast, macromolecular interactions which mediate the functions of E6, E7 and E2 are thought to be more difficult targets for small molecule therapy.

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Antipicornavirus Drugs: Current Status

Cited by 33 publications

References 68 publications

Viral diagnosis of neurological infection by RT multiplex PCR: A search for entero- and herpesviruses in a prospective study

Viral diagnosis of neurological infection by RT multiplex PCR: A search for entero- and herpesviruses in a prospective study

In Vitro Activity of Expanded-Spectrum Pyridazinyl Oxime Ethers Related to Pirodavir: Novel Capsid-Binding Inhibitors with Potent Antipicornavirus Activity

Molecular Targets for Human Papillomaviruses: Prospects for Antiviral Therapy

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