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Advances in Antiviral Drug Design
Number of Followers: 2

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ISSN (Print) 1075-8593
Published by Elsevier

[3203 journals]

List of Contributors
- Abstract: 2007
  Publication year: 2007
  Source:Advances in Antiviral Drug Design, Volume 5
  
  PubDate: 2012-12-17T18:13:09Z
Status Presens of Antiviral Drugs And Strategies: Part I: DNA Viruses and
Retroviruses
- Abstract: 2007
  Publication year: 2007
  Source:Advances in Antiviral Drug Design, Volume 5
  
  More than 40 compounds have been formally licensed for clinical use as antiviral drugs, and half of these are used for the treatment of HIV infections. The others have been approved for the therapy of herpesvirus (HSV, VZV, CMV), hepadnavirus (HBV), hepacivirus (HCV) and myxovirus (influenza, RSV) infections. New compounds are in clinical development or under preclinical evaluation, and, again, half of these are targeting HIV infections. Yet, quite a number of important viral pathogens (i.e. HPV, HCV, hemorrhagic fever viruses) remain in need of effective and/or improved antiviral therapies.
  
  PubDate: 2012-12-17T18:13:09Z
Status presens of antiviral drugs and strategies: Part II: RNA VIRUSES
(EXCEPT RETROVIRUSES)
- Abstract: 2007
  Publication year: 2007
  Source:Advances in Antiviral Drug Design, Volume 5
  
  More than 40 compounds have been formally licensed for clinical use as antiviral drugs, and half of these are used for the treatment of HIV infections. The others have been approved for the therapy of herpesvirus (HSV, VZV, CMV), hepadnavirus (HBV), hepacivirus (HCV) and myxovirus (influenza, RSV) infections. New compounds are in clinical development or under preclinical evaluation, and, again, half of these are targeting HIV infections. Yet, quite a number of important viral pathogens (i.e. HPV, HCV, hemorrhagic fever viruses) remain in need of effective and/or improved antiviral therapies.
  
  PubDate: 2012-12-17T18:13:09Z
Methylenecyclopropane Analogues of Nucleosides as Anti-herpes Agents
- Abstract: 2007
  Publication year: 2007
  Source:Advances in Antiviral Drug Design, Volume 5
  
  The current status of methylenecyclopropane analogues of nucleosides has been reviewed including synthetic methodology for the first- and second-generation analogues, antiviral activity with emphasis on β- and γ-herpesviruses, structure-activity relationships and mechanism of action. Fluoromethylenecyclopropanes, nucleotide analogues and phenyl phosphoralaninate (PPA) pronucleotides are also discussed.
  
  PubDate: 2012-12-17T18:13:09Z
Synthesis and antiviral evaluation of broad spectrum, orally active
analogs of cidofovir and other acyclic nucleoside phosphonates
- Abstract: 2007
  Publication year: 2007
  Source:Advances in Antiviral Drug Design, Volume 5
  
  PubDate: 2012-12-17T18:13:09Z
CCR5 antagonists for the treatment of HIV infection and AIDS
- Abstract: 2007
  Publication year: 2007
  Source:Advances in Antiviral Drug Design, Volume 5
  
  PubDate: 2012-12-17T18:13:09Z
The medicinal chemistry of the DATA and DAPY series of HIV-1
non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Abstract: 2007
  Publication year: 2007
  Source:Advances in Antiviral Drug Design, Volume 5
  
  This contribution presents an historical account of the medicinal chemistry of the DATA (diaryltriazine) and DAPY (diarylpyrimidine) series of inhibitors of HIV-1 reverse transcriptase (NNRTIs). The history extends over a period of more than 18 years, starting from 1987, and is still ongoing. The authors attempt to describe the often tortuous and unpredictable route that led from the virological screening of compounds, over serendipitous chemistry, X-ray crystallography, molecular modelling, animal pharmacokinetics, biochemistry and physical chemistry to the design and further development of highly potent anti-HIV compounds, three of which are now in advanced stages of clinical studies. The emphasis in this historical account is on the medicinal chemistry that led to the DATA and DAPY series of NNRTIs.
  
  PubDate: 2012-12-17T18:13:09Z
List of Contributors
- Abstract: 2003
  Publication year: 2003
  Source:Advances in Antiviral Drug Design, Volume 4
  
  PubDate: 2012-12-17T18:13:09Z
New Anti-HIV Agents in Preclinical or Clinical Development
- Abstract: 2003
  Publication year: 2003
  Source:Advances in Antiviral Drug Design, Volume 4
  
  Virtually all the compounds that are currently used (or have been the subject of advanced clinical trials) for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine and nucleotide reverse transcriptase inhibitors (NtRTIs) (i.e., tenofovir disoproxil fumarate); (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir and lopinavir. In addition to the reverse transcriptase and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, polynucleotides, and negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 (i.e., bicyclam (AMD3100) derivatives) and CCR5 (i.e., TAK-779 derivatives); (iii) virus-cell fusion, through binding to the viral envelope glycoprotein gp41 (T-20, T-1249); (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents (2,2′-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)); (v) proviral DNA integration, through integrase inhibitors such as 4-aryl-2,4-dioxobutanoic acid derivatives; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (flavopiridol, fluoroquinolones). Also, various new NRTIs, NNRTIs and PIs have been developed that possess, respectively: (i) improved metabolic characteristics (i.e., phosphoramidate and cyclosaligenyl pronucleotides by-passing the first phosphorylation step of the NRTIs), (ii) increased activity (“second” generation NNRTIs (i.e., TMC-125, DPC-083)) against those HIV strains that are resistant to the “first” generation NNRTIs, or (iii), as in the case of PIs, a different, modified peptidic (i.e., azapeptidic (atazanavir)) or non-peptidic scaffold (i.e., cyclic urea (mozenavir), 4-hydroxy-2-pyrone (tipranavir)). Non-peptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs.
  
  PubDate: 2012-12-17T18:13:09Z
Inhibitors of human immunodeficiency virus integration
- Abstract: 2003
  Publication year: 2003
  Source:Advances in Antiviral Drug Design, Volume 4
  
  PubDate: 2012-12-17T18:13:09Z
Non-peptidic protease inhibitors (NPPIs): Tipranavir
- Abstract: 2003
  Publication year: 2003
  Source:Advances in Antiviral Drug Design, Volume 4
  
  PubDate: 2012-12-17T18:13:09Z
Design of Neuraminidase Inhibitors as Anti-Influenza Virus Agents
- Abstract: 2003
  Publication year: 2003
  Source:Advances in Antiviral Drug Design, Volume 4
  
  PubDate: 2012-12-17T18:13:09Z
Six-membered Carbocyclic Nucleosides
- Abstract: 2003
  Publication year: 2003
  Source:Advances in Antiviral Drug Design, Volume 4
  
  PubDate: 2012-12-17T18:13:09Z
cycloSal-Pronucleotides—Design of the Concept, Chemistry, and
Antiviral Activity
- Abstract: 2003
  Publication year: 2003
  Source:Advances in Antiviral Drug Design, Volume 4
  
  PubDate: 2012-12-17T18:13:09Z
List of contributors
- Abstract: 1999
  Publication year: 1999
  Source:Advances in Antiviral Drug Design, Volume 3
  
  PubDate: 2012-12-17T18:13:09Z
From d-to l-nucleoside analogs as antiviral agents
- Abstract: 1999
  Publication year: 1999
  Source:Advances in Antiviral Drug Design, Volume 3
  
  PubDate: 2012-12-17T18:13:09Z
Orally bioavailable acyclic nucleoside phosphonate prodrugs: Adefovir
dipivoxil and bis(POC)PMPA
- Abstract: 1999
  Publication year: 1999
  Source:Advances in Antiviral Drug Design, Volume 3
  
  PubDate: 2012-12-17T18:13:09Z
HEPT: From an investigation of lithiation of nucleosides towards a
rational design of non-nucleoside reverse transcriptase inhibitors of
HIV-1
- Abstract: 1999
  Publication year: 1999
  Source:Advances in Antiviral Drug Design, Volume 3
  
  PubDate: 2012-12-17T18:13:09Z
Sialidase inhibitors as anti-influenza drugs
- Abstract: 1999
  Publication year: 1999
  Source:Advances in Antiviral Drug Design, Volume 3
  
  PubDate: 2012-12-17T18:13:09Z
Bicyclam derivatives as HIV inhibitors
- Abstract: 1999
  Publication year: 1999
  Source:Advances in Antiviral Drug Design, Volume 3
  
  PubDate: 2012-12-17T18:13:09Z
List of contributors
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Antiviral Drug Design, Volume 2
  
  PubDate: 2012-12-17T18:13:09Z
Antisense oligonucleotides as antiviral agents
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Antiviral Drug Design, Volume 2
  
  PubDate: 2012-12-17T18:13:09Z
Design and synthesis of S-adenosylhomocysteine hydrolase inhibitors as
broad-spectrum antiviral agents
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Antiviral Drug Design, Volume 2
  
  PubDate: 2012-12-17T18:13:09Z
Carbocyclic nucleosides
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Antiviral Drug Design, Volume 2
  
  PubDate: 2012-12-17T18:13:09Z
Comments on nucleotide delivery forms
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Antiviral Drug Design, Volume 2
  
  PubDate: 2012-12-17T18:13:09Z
Discovery and design of HIV protease inhibitors as drugs for treatment of
aids
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Antiviral Drug Design, Volume 2
  
  The protease encoded within the pol gene of human immunodeficiency virus (HIV) is essential for maturation of the newly budded virion to an infectious viral particle. For this reason, inhibitors of the HIV protease have been developed as possible drugs for treatment of acquired immunodeficiency syndrome (AIDS), a condition associated with HIV infection. The viral protease is a paradigm for rational drug design. It is a member of a well-characterized mechanistic set of proteases, the aspartyl enzymes, and therefore much is known by inference regarding its structure and mechanism. Yet, it is also unique among all known proteases in having a dimeric structure, and accordingly, it offers a selective target for drugs in humans. The monomeric units, identical, 99-residue polypeptides, each contribute symmetrically to the catalytic site, and the enzyme is a C 2-symmetric dimer. At the time of this writing, hundreds of structures have been solved crystallographically for the HIV-1 protease, both alone and in complexes with a wide spectrum of inhibitors, so the enzyme ranks among the best understood in terms of both structure and mechanism. The protease is also unique in its specificity, being able to hydrolyze almost any peptide bond, given an optimal distribution of amino acids in P4 through P4′, and accessibility to the bond in question. This specificity has been the basis for early development of protease inhibitors with noncleavable transition state inserts replacing the scissile bond pair. However, if an HIV protease inhibitor is to be successful as a drug for treatment of AIDS, it must not only be potent in blocking enzyme activity, but it must satisfy the usual criteria that define a useful therapeutic agent. The last 5 years have witnessed a transition from peptide-like inhibitors that are generally marginal as drugs because of poor solubility and/or bioavailability, to smaller, nonpeptide, organic molecules with enhanced pharmacokinetic properties. The process of protease inhibitor development has encompassed everything from serendipitous, classical screening approaches to de novo design. The latter achievement has been possible through an iterative cycle of crystallographic analysis, computer-assisted refinement and prediction, organic synthesis, and biological assays. In fact, this whole process of discovery of drugs designed to target the HIV protease represents a powerful alliance among numerous disciplines, including virology, biochemistry, molecular biology, X-ray crystallography, computer modeling, medicinal chemistry, pharmacology, and applied medicine. This chapter focuses on this process, highlighting those protease inhibitors that have been brought forward for clinical trials, and providing some early results in the clinics. Some discussion is also included of mutations in the protease, which have been documented in viral strains that show resistance to protease inhibitor drugs.
  
  PubDate: 2012-12-17T18:13:09Z