Antiviral drugs in current clinical use

Clercq, Erik De

doi:10.1016/j.jcv.2004.02.009

Cited by 875 publications

(562 citation statements)

References 15 publications

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“…The 1,2,4-triazole, as well found to exhibit antiasthmatic [14] , antiviral (ribavirin) [15] , antifungal (fluconazole) [16] , antimicrobial [17,18] , antibacterial [19][20][21] , insecticidal [22] , hypnotic [23] , cytotoxic [24] , antitubercular [25] and hypotensive [26,27] activities. This moiety was also found in potent agonist and antagonist receptor ligands [28,29] in HIV-1 protease inhibitors [30] and in thrombin inhibitors [31] .…”

Section: Research Papermentioning

confidence: 99%

Design and Synthesis of New Bioactive 1,2,4-Triazoles, Potential Antitubercular and Antimicrobial Agents

Singh¹,

Kashaw²,

Mishra³

et al. 2018

pharmaceutical-sciences

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Section: Research Papermentioning

confidence: 99%

Design and Synthesis of New Bioactive 1,2,4-Triazoles, Potential Antitubercular and Antimicrobial Agents

Singh¹,

Kashaw²,

Mishra³

et al. 2018

pharmaceutical-sciences

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“…), IFN also promotes cell survival through a nuclear factor B-dependent pathway (2)(3)(4). IFN is used to treat various human malignancies (chronic myeloid leukemia, non-Hodgkin lymphomas, Kaposi sarcoma, hairy cell leukemia, multiple myeloma, and malignant melanoma), viral infections, as well as various other diseases (5,6). However, only a fraction of patients are responsive to IFN therapy, and many patients eventually develop resistance after chronic IFN exposure.…”

Section: Ifnmentioning

confidence: 99%

Interferon-resistant Daudi Cell Line with a Stat2 Defect Is Resistant to Apoptosis Induced by Chemotherapeutic Agents

Fan

Kim

et al. 2009

Journal of Biological Chemistry

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Interferon-␣ (IFN␣) has shown promise in the treatment of various cancers. However, the development of IFN resistance is a significant drawback. Using conditions that mimic in vivo selection of IFN-resistant cells, the RST2 IFN-resistant cell line was isolated from the highly IFN-sensitive Daudi human Burkitt lymphoma cell line. The RST2 cell line was resistant to the antiviral, antiproliferative, and gene-induction actions of IFN␣. Although STAT2 mRNA was present, STAT2 protein expression was deficient in RST2 cells. A variant STAT2 mRNA, which resulted from alternative splicing within the intron between exon 19 and 20, was expressed in several human cell lines but at relatively high levels in RST2 cells. Most importantly, the RST2 line showed an intrinsic resistance to apoptosis induced by a number of chemotherapeutic agents (camptothecin, staurosporine, and doxorubicin). Expression of STAT2 in RST2 cells not only rescued their sensitivity to the biological activities of IFNs but also restored sensitivity to apoptosis induced by these chemotherapeutic agents. The intrinsic resistance of the RST2 cells to IFN as well as chemotherapeutic agents adds a new dimension to our knowledge of the role of STAT2 as it relates to not only biological actions of IFN but also resistance to chemotherapyinduced apoptosis. IFN2 ␣/␤ regulates a number of cellular responses, such as proliferation, differentiation, and development (1). Although IFN triggers the death of some tumor cells by inducing proapoptotic proteins (tumor necrosis factor-related apoptosis-inducing ligand, PKR, etc.), IFN also promotes cell survival through a nuclear factor B-dependent pathway (2-4). IFN is used to treat various human malignancies (chronic myeloid leukemia, non-Hodgkin lymphomas, Kaposi sarcoma, hairy cell leukemia, multiple myeloma, and malignant melanoma), viral infections, as well as various other diseases (5, 6). However, only a fraction of patients are responsive to IFN therapy, and many patients eventually develop resistance after chronic IFN exposure. The underlying mechanism for IFN resistance is still unclear, but it is reasonable to suggest that genetic variation and selection during prolonged IFN exposure may reflect IFN signaling defects.IFN binds to its cell surface receptor resulting in the activation of JAK1 and TYK2 nonreceptor protein-tyrosine kinases, which phosphorylate STAT proteins (7). Phosphorylated STAT1 and STAT2 in a complex with IRF9 bind to a conserved IFN stimulus-response element (ISRE) present in the promoters of hundreds of IFN-stimulated genes (ISGs) inducing their expression. Mutant cell lines with defined signaling defects have made significant contributions in elucidating the IFN-activated JAK/STAT signal transduction pathway (7,8). Such IFN-resistant mutants were isolated after multiple rounds of chemical mutagenesis and selection of IFN-resistant mutants. However, this procedure does not mimic in vivo what happens to patients who are subjected to long term IFN treatment. Moreover, these IFN-resistant cells ...

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“…Recently, it was postulated that a variation of a single amino acid of the DNA polymerase is strongly associated with neurological versus non-neurological disease outbreaks (Nugent et al, 2006). This may have an implication on the susceptibility of various isolates to anti-herpetic compounds as many of these compounds act on the DNA polymerase (De Clercq, 2004). Finally, the drug should be safe and devoid of adverse effects.…”

Section: Introductionmentioning

confidence: 99%

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Garré

Meulen

Nugent

et al. 2007

Veterinary Microbiology

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Equine herpesvirus 1 (EHV-1) is an important equine pathogen that causes respiratory disease, abortion, neonatal death and paralysis. Although vaccines are available, they are not fully protective and outbreaks of disease may occur in vaccinated herds. Therefore, there is an urgent need for effective antiviral treatment. For three abortigenic (94P247, 97P70 and 99P96) and three neuropathogenic isolates (97P82, 99P136 and 03P37), the effect of acyclovir, ganciclovir, cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) and foscarnet on plaque number was studied. Additionally, for isolate 97P70, the effect on plaque size was investigated. Ganciclovir was most potent in reducing plaque number, followed by PMEDAP and acyclovir. Adefovir and cidofovir were less effective and foscarnet was the least effective compound. There were no differences detected for acyclovir, ganciclovir, adefovir and PMEDAP between the abortigenic and neuropathogenic isolates. One abortigenic isolate (99P96) was more susceptible to cidofovir and two neuropathogenic isolates (99P136 and 03P37) were less susceptible to foscarnet. For isolate 97P70, all compounds resulted in a significant reduction of plaque size. The most remarkable effect was observed for cidofovir. It was 40-fold more effective in reducing plaque size than in reducing plaque number. In conclusion, ganciclovir was the most potent compound and therefore, may be a valuable candidate for the treatment of EHV-1 infections in horses. The antiviral effect of foscarnet on plaque number was highly dependent on the viral isolate tested. Therefore, it is no valuable antiviral for the treatment of herpesvirus-infections. Cidofovir, although less effective in reducing plaque number, had a strong effect on plaque size. #

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Antiviral drugs in current clinical use

Cited by 875 publications

References 15 publications

Design and Synthesis of New Bioactive 1,2,4-Triazoles, Potential Antitubercular and Antimicrobial Agents

Design and Synthesis of New Bioactive 1,2,4-Triazoles, Potential Antitubercular and Antimicrobial Agents

Interferon-resistant Daudi Cell Line with a Stat2 Defect Is Resistant to Apoptosis Induced by Chemotherapeutic Agents

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

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