Article

Antiviral drugs in current clinical use.

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Journal of Clinical Virology (Impact Factor: 3.47). 07/2004; 30(2):115-33. DOI: 10.1016/j.jcv.2004.02.009
Source: PubMed

ABSTRACT The current armamentarium for the chemotherapy of viral infections consists of 37 licensed antiviral drugs. For the treatment of human immunodeficiency virus (HIV) infections, 19 compounds have been formally approved: (i) the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; (ii) the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir disoproxil fumarate; (iii) the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine, delavirdine and efavirenz; (iv) the protease inhibitors saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir (combined with ritonavir at a 4/1 ratio) and atazanavir; and the viral entry inhibitor enfuvirtide. For the treatment of chronic hepatitis B virus (HBV) infections, lamivudine as well as adefovir dipivoxil have been approved. Among the anti-herpesvirus agents, acyclovir, valaciclovir, penciclovir (when applied topically), famciclovir, idoxuridine and trifluridine (both applied topically) as well as brivudin are used in the treatment of herpes simplex virus (HSV) and/or varicella-zoster virus (VZV) infections; and ganciclovir, valganciclovir, foscarnet, cidofovir and fomivirsen (the latter upon intravitreal injection) have proven useful in the treatment of cytomegalovirus (CMV) infections in immunosuppressed patients (i.e. AIDS patients with CMV retinitis). Following amantadine and rimantadine, the neuraminidase inhibitors zanamivir and oseltamivir have recently become available for the therapy (and prophylaxis) of influenza virus infections. Ribavirin has been used (topically, as aerosol) in the treatment of respiratory syncytial virus (RSV) infections, and the combination of ribavirin with (pegylated) interferon-alpha has received increased acceptance for the treatment of hepatitis C virus (HCV) infections.

0 Followers
 · 
245 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper describes the screening of different South American plant extracts and fractions. Aqueous and organic extracts were prepared and tested for antiherpetic (HSV-1, KOS and 29R strains) and antirabies (PV strain) activities. The evaluation of the potential antiviral activity of these extracts was performed by using an MTT assay for HSV-1, and by a viral cytopathic effect (CPE) inhibitory method for rabies virus (RV). The results were expressed as 50% cytotoxicity (CC(50)) for MTT assay and 50% effective (EC(50)) concentrations for CPE, and with them it was possible to calculate the selectivity indices (SI = CC(50)/EC(50)) of each tested material. From the 18 extracts/fractions tested, six extracts and four fractions showed antiviral action. Ilex paraguariensis, Lafoensia pacari, Passiflora edulis, Rubus imperialis and Slonea guianensis showed values of SI > 7 against HSV-1 KOS and 29-R strains and Alamanda schottii showed a SI of 5.6 against RV, PV strain.
    Phytotherapy Research 10/2007; 21(10):970-4. DOI:10.1002/ptr.2198 · 2.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV envelope glycoprotein transmembrane subunit gp41 plays a critical role in the fusion between viral and target cell membranes. Upon gp120 binding to CD4 and a coreceptor (CCR5 or CXCR4), gp41 changes its conformation by forming N-helix trimer between N-heptad repeats (NHRs) and then six-helix bundle between the N-trimer and the C-heptad repeats (CHRs). Peptides derived from the NHR and CHR of gp41 extracellular region have demonstrated potent inhibitory activity on the HIV mediated cell fusion. One of these peptides, T-20, became the first success of a new class of anti-HIV agents, named HIV entry inhibitors. However, a relatively long peptide such as T-20 suffers from several limitations including lack of oral bioavailability and high cost of production. Great efforts have been made to develop alternative peptides and proteins with improved anti-HIV-1 activity, increased bioavailability and reduced cost of production. The most promising approach is the development of small molecule HIV entry inhibitors targeting gp41. Any molecule that blocks the process of NHR homotrimerization and the six-helix bundle formation by targeting the gp41 NHR, NHR trimer and CHR may inhibit HIV-mediated membrane fusion. The progress in development of those anti-HIV agents targeting gp41, from polypeptides to small-molecule compounds, is reviewed.
    Current pharmaceutical design 02/2007; 13(2):143-62. DOI:10.2174/138161207779313722 · 3.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cytomegalovirus (CMV) infection can cause severe disease in immunocompromised individuals, with CMV pneumonia, most commonly seen in lung or bone marrow transplant recipients, carrying a particularly high fatality rate. Early and accurate diagnosis of CMV pneumonia is therefore critical. Current diagnostic tests for CMV pneumonia in bronchoalveolar lavage (BAL) specimens are either insensitive or poor prognostic indicators of disease. We therefore examined nucleic acid sequence-based amplification (NASBA) assays for CMV transcripts in BAL for the prediction of CMV pneumonia and associated diseases. A total of 220 BAL specimens from lung transplant recipients and other patients with suspected viral pneumonia were studied. Ninety-nine samples had previously tested positive for CMV by shell vial (SV) culture, while the other 121 had tested negative. All specimens were assayed for CMV pp67 and immediate early (IE) transcripts by NASBA. Results were correlated with evidence of concurrent or subsequent CMV pneumonia, rejection, and infection with other microbes. From a total of 220 BAL specimens, 27 tested positive for pp67 mRNA, 25 tested positive for IE mRNA, and 17 tested positive for both. Only 10 specimens tested positive for CMV by either or both NASBA assays while testing negative by SV assay. However, 74 specimens were SV positive but negative in both NASBA assays. Detection of CMV by any of the three methods was associated with an increased prevalence of pneumonia (i.e., pulmonary interstitial inflammation with radiographic or clinical evidence of lung injury), but not with pulmonary CMV pathology. Detection of CMV by SV was associated with moderate to severe graft rejection. There was no evidence of increased bacterial or fungal pulmonary infections associated with a positive CMV result by any of the three assays. Detection of either CMV pp67 or IE mRNA transcripts by NASBA in BAL specimens can occasionally identify CMV infections that are negative by conventional shell vial culture, but does not have sufficient sensitivity or positive predictive value to be employed routinely for pre emptive management of pulmonary CMV disease in transplant recipients.
    Journal of Clinical Virology 01/2007; 37(4):258-64. DOI:10.1016/j.jcv.2006.08.010 · 3.47 Impact Factor

Preview

Download
12 Downloads
Available from