Check out our New Publishers' Select for Free Articles

Antiviral Research (v.82, #2)

Biophysical Mechanisms in Microbicide Pharmacokinetics by David Katz; Marcus Henderson; Bonnie Lai; Anthony Geonnotti; Jennifer Peters (pp. a74).

Motor Unit Number Estimation as a Therapeutic Marker in Acute and Persistent West Nile Virus Infection in Hamsters by John D. Morrey; Venkatraman Siddharthan; Hong Wang; Neil E. Motter; Jeffery O. Hall; Robert D. Skinner; Ramona T. Skirpstunas (pp. a72).

Virtual Reality Applications in Antiviral Drug Design by Nicola Zonta; Andrea Brancale (pp. a74).

Targeting Hepatitis C Virus NS2An Unusual Protease with Multiple Functions by Thomas Pietschmann Ph.D. (pp. a19).

Antiviral Activity of Tetrahydro-2(1H)-Pyrimidinones and Related Compounds: Classification SAR Study by V. Kuz’min (pp. a61).

Antiviral Activity of Carbohydrate Binding Agents (CBAS) and the Role of DC-SIGN in Dengue Virus and HIV Infection by Marijke Alen; Suzanne J.F. Kaptein; Tine De Burghgraeve; Johan Neyts; Jan Balzarini; Dominique Schols (pp. a22).

Effects of Antivirals via Intratympanic Delivery in GPCMV-related Hearing Loss by Jonette Ward; Daniel Choo (pp. a53).

Novel Imino Sugar Derivatives Demonstrate Potent Antiviral Activity against Dengue Virus by Jinhong Chang; Lijuan Wang; Dongling Ma; Xiaodong Xu; Wouter Schul; Pei-Yong Shi; Peter M. Mason; Nigel Bourne; Robert Moriarty; Ju-Tao Guo; Timothy M. Block (pp. a72-a73).

From β-Amino-γ-Sultone to New Bicyclic Pyridine and Pyrazine Heterocyclic Systems: Discovery of a Novel Class of HIV-1 Non-nucleoside Inhibitors by Sonsoles Velazquez; Sonia De Castro; Jan Balzarini; María-Jose Camarasa (pp. a26-a27).

The Development of HIV-1 NCP7 Inhibitors as Components in Combination Topical Microbicides by Karen Watson; Kathleen Powers; Lu Yang; Tracy Hartman; Robert Buckheit Jr. (pp. a66-a67).

Comparative Efficacy of Treatment with CMX001 Versus Acyclovir in BALB/c Mice Infected with Herpes Simplex Virus by Debra Quenelle; Mark Prichard; Emma Harden; Deborah Collins; Terri Rice; George Painter; Alice Robertson; Earl Kern (pp. a51-a52).

Comparative Study of the Efficacy of Low- and High-Molecular Inhibitors of Influenza Virus Hemagglutinin by S. Rak; E. Goncharova; I. Vinogradov; E. Ryabchikova; A. Chinarev; A. Tuzikov; N. Bovin; A. Ryzhikov (pp. a35).

CADA, a Potential Anti-HIV Microbicide that Specifically Targets the Cellular CD4 Receptor by Kurt Vermeire; Thomas Bell; Roger Le Grand; Joachim Brouwers; Patrick Augustijns; Dominique Schols (pp. a66).

Anti-cytomegalovirus Activity of Membranotropic Polyacidic Agents Effects In Vitro by M. Pavlova; A. Serbin; N. Fedorova; E. Karaseva; E. Klimova; A. Kushch (pp. a50-a51).

Murine Model of Recurrent Vaginal HSV-2 Shedding and Effect of Acyclovir by Rhonda Cardin; Nicholas Farley; Fernando Bravo; Julie Earwood; Nancy Sawtell; David Bernstein (pp. a69).

The Complexities of Hepatitis C Virus Entry by Jane McKeating Ph.D. (pp. a19).

A Strong Dominant Negative Mutation in the HIV-1 Gag Protein Defines a New Drug Target by Ronald Swanstrom Ph.D. (pp. a43).

Identification of a Small-molecule Antiviral with Broad-spectrum Application to Multiple, Lethal Virus Types by Abdul Yunus; Travis Warren; Kelly Warfield; Sven Enterlein; Shaojing Chang; Hanwen Mao; Javad Aman; Sina Bavari; Michael Goldblatt; Michael Kinch (pp. a74-a75).

Anti-HIV-1 Activity of A3G is Enhanced by HSP70 by Ryuichi Sugiyama; Yuichiro Habu; Haruki Naganuma; Hiroshi Koseki; Ayako Furukawa; Takashi Nagata; Masato Katahira; Hiroshi Takaku (pp. a26).

Inhibition of Herpesvirus Replication With 5-Iodo-4′-Thio-2′-Deoxyuridine by Mark Prichard; Debra Quenelle; Caroll Hartline; Emma Harden; Geraldine Jefferson; Samuel Frederick; Terri Rice; Deborah Collins; Kamal Tiwari; Joseph Maddry; Richard Whitley; John Secrist; Earl Kern (pp. a67).

The Microbicide Pipeline: Clinical Development Success and Failure by Joseph Romano Ph.D. (pp. a74).

Plenary: Filoviral Minigenome systems and iVLPs as tools for antiviral research by Stephan Becker (pp. a70).

Using the C57BL/6 and SKH1 Strains to Evaluate the Efficacy of CMX001 Following Lethal Respiratory Infections with Ectromelia Virus by Scott Parker; Christina Oberle; Ed Hembrador; Jill Schriewer; Geroge Painter; Randall Lanier (pp. a73).

Immediate and Persistent Anti-HIV-1 Activity of the Biguanide-based Compound NB325 Involves Specific Interactions with the Viral Co-receptor CXCR4 by Nina Thakkar; Vanessa Pirrone; Shendra Passic; Mohamed Labib; Robert Rando; Brian Wigdahl; Fred Krebs (pp. a26).

Future Conferences (pp. a83).

In vitro transport, activation and antiviral evaluation of new HPMPA prodrugs synthesized on a solid support by Ivan S. Krylov; Larryn W. Peterson; Boris A. Kashemirov; Julie Breitenbach; Kathy Borysco; John C. Drach; Jae Seung Kim; John M. Hilfinger; Charles E. McKenna (pp. a75).

Characterization of the Mechanism of Action of PG-301029: A Novel Late Stage Inhibitor of HCV Replicon Replication by Todd Parsley; Lu Yang; Robert Buckheit Jr. (pp. a31).

EBNA1—A virally encoded protein binds cellular host promoters in a unique sequence and directly interferes with cellular gene expression. Implications for genomics approaches in drug design by Allon Canaan; Vincent Schulz; Milind Mahajan; Alexander Urban; Sherman Weissman (pp. a69-a70).

Study of Anti-Epstein–Barr Virus Activity of Novel Fluorinated Heterocyclic Nucleoside Analogues by N. Nesterova; Yu. Shermolovich; S. Zagorodnya; A. Golovan; O. Kanishchev; G. Baranova (pp. a50).

A Heterocyclic Molecule with Significant Activity Against Dengue Virus by Vasu Nair; Guochen Chi; Qingning Shu; Justin Julander; Donald Smee (pp. a62).

Induction of Lytic Cytotoxicity by NF-(B Inhibitors in Epstein-Barr Virus-associated Gastric Carcinoma Cells by Paula Ordonez Suarez; Chihaya Koriyama; Yoshito Eizuru; Suminori Akiba (pp. a50).

Full Author Index – Abstract Number (Bold number signifies first author) (pp. a76-a81).

Comparison of Various Combination Therapies for the Treatment of Yellow Fever Virus by Justin Julander; Don Smee; John Morrey; Yousuke Furuta (pp. a29).

Phenotyping Human Cytomegalovirus Drug Resistance Mutations Using a Recombinant Virus Incorporating EGFP by Meike Chevillotte; Hans A. Kestler; Thomas Mertens; Jens von Einem (pp. a47).

Escaping Development of Drug-Resistant Mutants: Basis for Effective Chemotherapy of Enterovirus Infections by Angel S. Galabov; Ralitsa Vassileva-Pencheva; Ivanka Nikolova; Boris Atanasov (pp. a38).

Derivatives of Tunicamycin as Effective Inhibitors of Classical Swine Fever Virus by Ewelina Krol; Ilona Wandzik; Boguslaw Szewczyk; Grzegorz Grynkiewicz; Wieslaw Szeja (pp. a40).

New Methods to Identify and Analyze HCV Helicase Inhibitors by David Frick Ph.D. (pp. a19).

Study of the Retention of Metabolites of 4′-ED4T, A Novel Anti-HIV-1 Thymidine Analog, in Cells by Xin Wang; Hiromichi Tanaka; Masanori Baba; Yung-Chi Cheng (pp. a27).

Hepatitis C Virus NS5A Protein In Vitro Modulates Template Selection by the RNA-dependent RNA Polymerase by Olga Ivanova; Vera Tunitskaya; Alexander Ivanov; Vladimir Mitkevich; Vladimir Prassolov; Alexander Makarov; Marina Kukhanova; Sergey Kochetkov (pp. a28-a29).

Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: Current state of the art by Karl Y. Hostetler (pp. a84-a98).

Although the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir are approved for treating human cytomegalovirus, hepatitis B and HIV infections, respectively, their utility is limited by low oral bioavailability, renal toxicity and poor cell penetration. Research over the past decade has shown that these undesirable features can be eliminated by esterifying the compounds with an alkoxyalkyl group, in effect disguising them as lysophospholipids. In this modified form, the drugs are readily taken up in the gastrointestinal tract and have a prolonged circulation time in plasma. The active metabolite also has a long half life within cells, permitting infrequent dosing. Because these modified drugs are not recognized by the transport mechanisms that cause the accumulation of acyclic nucleoside phosphonates in renal tubular cells, they lack nephrotoxicity. Alkoxyalkyl esterification also markedly increases the in vitro antiviral activity of acyclic nucleoside phosphonates by improving their delivery into cells. For example, an alkoxyalkyl ester of cyclic-cidofovir, a less soluble compound, retains anti-CMV activity for 3 months following a single intravitreal injection. Two of these novel compounds, hexadecyloxypropyl-cidofovir (CMX001) and hexadecyloxypropyl-tenofovir (CMX157) are now in clinical development. This article focuses on the hexadecyloxypropyl and octadecyloxyethyl esters of cidofovir and (S)-HPMPA, describing their synthesis and the evaluation of their in vitro and in vivo activity against a range of orthopoxviruses, herpesviruses, adenoviruses and other double-stranded DNA viruses. The extension to other nucleoside phosphonate antivirals is highlighted, demonstrating that this novel approach can markedly improve the medicinal properties of these drugs.

Keywords: Abbreviations; Ad5; adenovirus type 5; ALT; alanine aminotransferase; AUC; area under curve; CDV; cidofovir; CDVp; cidofovir monophosphate; CDVpp; cidofovir diphosphate; CMV; cytomegalovirus; cPr-DAP; N; ⁶; -cyclopropyl-2,6-diaminopurine; CPX; cowpox; dATP; deoxyadenosine triphosphate; dCTP; deoxycytosine triphosphate; ECTV; ectromelia virus; GCV; ganciclovir; HBV; hepatitis B virus; HCMV; human cytomegalovirus; HD; hexadecyl; HDP; hexadecyloxypropyl; HDP-CDV; hexadecyloxypropyl-cidofovir; HDP-PMEDAP; hexadecyloxypropyl-9-(2-phosphono-methoxyethyl)-2,6-diaminopurine; HDP-PMPA; hexadecyloxypropyl-(; R; )-9-(2-phosphono-methoxypropyl)adenine; HHV; human herpes virus; HIV; human immunodeficiency virus; HPMP; 3-hydroxy-2-(phosphonomethoxy)propyl; HPMPA; (; S; )-9-(3-hydroxy-2-phosphono-methoxypropyl)adenine; HPMPAp; HPMPA monophosphate; HPMPApp; HPMPA diphosphate; HPPMP; 3-hydroxy-2-(phosphophosphonomethoxy)propyl; HPMPC; (; S; )-1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine (cidofovir); HPMPDAP; (S)-9-(3-hydroxyl-2-phosphono-methoxypropyl)-2,6-diaminopurine; HPV; human papilloma virus; IHD; the IHD strain of vaccinia virus; LPC; lysophosphatidylcholine; NRTI; nucleoside reverse transcriptase inhibitor; ODBG; 1-; O; -octadecyl-2-; O; -benzyl-sn-glycerol; ODE-CDV; octadecyloxyethyl-cidofovir; PBMC; peripheral blood mononuclear cells; PC; phosphatidylcholine; Pfu; plaque forming unit; PME; 2-(phosphonomethoxy)ethyl; PMEA; 9-(2-phosphonylmethoxyethyl)adenine; PMEDAP; 9-(2-phosphonomethoxyethyl)-2,6-diaminopurine; PMP; 3-hydroxy-2-(phosphonomethoxy)propyl; PMPA; (; R; )-9-(2-phosphonomethoxypropyl)adenine; PPen; 5-phosphono-pent-2-en-1-yl; PPM; phosphonopropoxymethyl; PPMDAP; phosphonopropoxymethyl-2,6,-diaminopurine; RPV; rabbitpox virus; SCID; severe combined immunodeficiency; TCID; tissue culture infectious dose; VV; vaccinia virus; VV-LED; vaccinia virus-Lederle; VV-WR; vaccinia virus Western Reserve; VZV; varicella zoster virus; Wt; wild typeLysophospholipids; Ether lipids; Prodrugs; Alkoxyalkyl esters; Hexadecyloxypropyl-cidofovir; Hexadecyloxypropyl-tenfovir; Hexadecyloxypropyl-(; S; )-HPMPA; Vaccinia virus; Cowpoxvirus; Ectromelia virus; Cytomegalovirus; Adenovirus; HIV-1; Hepatitis B virus

Combinations of 5-Iodo-4′-thio-2′-deoxyuridine and ST-246 or CMX001 Synergistically Inhibit Orthopoxvirus Replication In Vitro by Kathy Keith; Shalisa Sanders; Kamal Tiwari; Joseph Maddry; John Secrist; Robert Jordan; Dennis Hruby; Randall Lanier; George Painter; Earl Kern; Mark Prichard (pp. a33-a34).

Pradimicin-S is a Highly Soluble Non-peptidic Small-size Carbohydrate-binding Antibiotic that may Qualify as a Potential Drug Lead for HIV Treatment by J. Balzarini; K. François; K. Van Laethem; B. Hoorelbeke; J. Auwerx; S. Liekens; Y. Igarashi; T. Oki; D. Schols (pp. a44).

Inhibition of Influenza Virus Replication: Discovery and Development of Therapeutic Compounds which Suppress Viral RNA Synthesis by Tracy Hartman; Robert Buckheit Jr. (pp. a33).

HIV-1 Gag Matrix Protein Fragments and Polyacid Conjugates Designed for the HIV Inhibition by E. Karaseva; A. Serbin; I. Rodionov; A. Vasiliev; V. Abramov; O. Alikhanova (pp. a59).

In Vitro Activity and In Vivo Pharmacokinetics of Highly Potent Phosphoramidate Nucleoside Analogue Inhibitors of Hepatitis C NS5B by J. Hutchins; S. Chanberlain; C. Chang; B. Ganguly; E. Gorovits; A. Hall; G. Henson; A. Kolykhalov; Y. Liu; J. Muhammad; P. Perrone; A. Gilles; S. Holl; K. Madela; C. McGuigan; J. Patti (pp. a28).

Design of Intravaginal Ring for Simultaneous Delivery of Antiretroviral Drugs by Todd Johnson; Kavita Gupta; Patrick Kiser (pp. a74).

Comparative Study of the Genetic Barrier and Pathways Towards Resistance of Selective Inhibitors of HCV Replication by Inge Vliegen; Leen Delang; Johan Neyts (pp. a21).

Design of Artificial Polyepitope DNA Vaccine Constructs for Eliciting of HIV-Specific CD8+ CTL Responses by Svetlana Oreshkova; Sergey Bazhan; Pavel Belavin; Tatyana Ilyicheva; Sergey Seregin; Alexander Ilyichev; Larisa Karpenko (pp. a25).

Antiviral Activity of Monoterpene Components of Essential Oils Against Herpes Simplex Virus by Akram Astani; Jürgen Reichling; Paul Schnitzler (pp. a46).

Conserved Retinoblastoma Protein-binding Motifs in Human Cytomegalovirus UL97 Minimally Impact Viral Replication But can Affect Susceptibility to Maribavir by Caroll Hartline; Rachel Gill; Samuel Frederick; Sunwen Chou; Mark Prichard (pp. a48).

West Nile Virus Helicase: Homology Modeling and Docking Studies by Mohammed Khedr; Andrea Brancale (pp. a60).

2′-Deoxy-nucleoside Analogs can be Potent Dual Inhibitors of HCV and HIV Replication with Selectivity against Human Polymerases by Klaus Klumpp; Guoping Su; Vincent Leveque; Jerome Deval; Gabrielle Heilek; Sonal Rajyaguru; Yu Li; Julie Q. Hang; Han Ma; Nicole Inocencio; Genadiy Kalayanov; Anna Winqvist; David B. Smith; Nick Cammack; Nils Gunnar Johansson; Isabel Najera (pp. a19).

Using the Conrad Testing Algorithm to Evaluate the Cytotoxicity and Anti-HIV-1 Activity of Candidate Microbicide Compounds by Shendra Passic; Vanessa Pirrone; Brian Wigdahl; Gustavo Doncel; Fred Krebs (pp. a65).

Interactions Between the Human Oligopeptide Transporter, hPepT1 and Serine Side-chain-linked Cidofovir Prodrugs by Monica Sala-Rabanal; Larryn W. Peterson; Michaela Serpi; Ivan S. Krylov; Boris A. Kashemirov; Jae Seung Kim; Stefanie Mitchell; John M. Hilfinger; Charles E. McKenna (pp. a53-a54).

Structural Basis of the Disoxaril Resistance and Dependence of Coxsackievirus B1 by Ivanka Nikolova; Angel S. Galabov; Rumena Petkova; Stoyan Chakarov; Boris Atanasov (pp. a41).

Expression of Infectious Bursal Disease Virus (IBDV) Polyprotein and VP4 Protease by Phillia Vukea; Alain Boulange; Theresa Coetzer (pp. a55).

Predictive Factors to Response to Interferon Therapies for Treatment-naive Patients Infected with Hepatitis C Virus in Islamabad and Vicinity Areas: A Study from Pakistan by Abida Raza; Hafsa Aziz; Javed Irfan (pp. a31).

Nucleoside Phosphonate Analogues Modified by Lipophilic Cage Moiety as Potential Antiviral Agents by Yuri Klimochkin; Marina Leonova; Alexander Reznikov; Andrey Shiraev; Eugene Golovin; Eugene Belanov (pp. a60).

4,4-Disubstituted Cyclohexylamine based CCR5 Chemokine Receptor Antagonists as Anti-HIV-1 agents by Maosheng Duan; Wieslaw Kazmierski; Christopher Aquino; Rob Ferris; Terry Kenakin; Chris Watson; Pat Wheelan (pp. a57).

Clinical Failures of Select Polyanionic Microbicide Candidates may be Predicted by In Vitro Enhancement of HIV-1 Infection by Vanessa Pirrone; Shendra Passic; Brian Wigdahl; Fred Krebs (pp. a65-a66).

Cinnamon Fraction Neutralizes Avian Influenza H5N1 Both In Vitro and In Vivo by Michael Ovadia; Immanuel Kalily; Emily Bernstein (pp. a35).

CycloSaligenyl-di-d4TMP: Highly Loaded CycloSal-pronucleotides that Release Two Equivalents of Nucleotides and Leaving One Masking Unit by Chris Meier; Nicolas Gisch; Ducho Christian; Balzarini Jan (pp. a61).

In Vitro Anti-Influenza Virus Effect of a Protease Inhibitor from a Streptomyces Strain by Julia Serkedjieva; Lidia Angelova-Duleva; Iskra Ivanova (pp. a36).

Identification of the Type of Cells Responsible for Transfer of Herpes Simplex Virus (HSV) and Vaccinia Virus (VACV) Infection to Epithelial Cells Grown in 3D by Graciela Andrei; Dirk Daelemans; Els Vanstreels; Sophie Duraffour; Joos Van Den Oord; Erik De Clercq; Robert Snoeck (pp. a68).

Pre-clinical Development of IQP-0410, a Highly Potent Dual-acting Agent for the Therapy of HIV-1 Infection by Nick Kaludov; Karen Watson; Robert Buckheit Jr. (pp. a46).

Identification and Characterization of Pyrimidinediones as Potent Non-nucleoside Reverse Transcriptase Inhibitors of Hepatitis B virus by Lu Yang; Todd Parsley; Robert Buckheit Jr. (pp. a32).

Novel Broad-Spectrum Biopharmaceuticals: From HIV-1 to Pandemic Influenza A Virus by François Jean; Vesna Posarac; Peter Cheung; Martine Boutin; Heather Braybrook; Richard Harrigan (pp. a70-a71).

l-Analogs of 1-Beta-d-Ribofuranosyl-2-Bromo-5,6-Dichlorobenzimidazole (BDCRB) Inhibit Human Herpesvirus-6 Replication by Mark Prichard; Samuel Frederick; Shannon Daily; Kathy Borysko; Julie Breitenbach; Leroy Townsend; John Drach (pp. a51).

HiT QSAR Study of Antivirals’ Bioavailability by Anatoly Artemenko; Eugene Muratov; Victor Kuz’min; Maxim Kulinskij; Irina Borisuk; Nikolay Golovenko; Alexander Tropsha (pp. a56).

Antiviral compounds; Bioavailability; Virtual screening

Bioreversible Protection of Nucleosidediphosphates—Synthesis and Properties by Tilmann Schulz; Henning J. Jessen; Jan Balzarini; Chris Meier (pp. a63).

Compounds that Target Host Cell Enzymes Prevent Varicella-zoster Virus Replication In Vitro, Ex Vivo, and in SCID-hu Mice by J. Rowe; R. Greenblatt; D. Liu; J. Moffat (pp. a52).

Beautiful Biology But Bad Chemistry: Recognizing Chemistry Problems Earlier Rather Than Later by Christopher Lipinski Ph.D. (pp. a19).

Characterization of Cowpox Virus (CPV) Mutants Arising under Pressure with Different Acyclic Nucleoside Phosphonates by Graciela Andrei; Pierre Fiten; Erik De Clercq; Ghislain Opdenakker; Robert Snoeck (pp. a53).

In Vivo Efficacy Evaluation of Vaccines Against H5N1 Influenza Virus by Nutan Mytle (pp. a71).

ZNRD1 as a Host Cellular Factor Influencing HIV-1 Replication by Ester Ballana; Jordi Senserrich; Eduardo Pauls; Josep Maria Mercader; Bonaventura Clotet; Lidia Ruiz; Jorge Gallego; Frédéric Uyttebroeck; Amalio Telenti; Angela Cuiffi; José A. Esté (pp. a45).

Selection and Characterization of (S)-1-[3-Hydroxy-2-(Phosphonomethoxypropyl)-2,6-Diaminopurine [HPMPDAP] Resistant Camelpox Viruses by Sophie Duraffour; Robert Snoeck; Pierre Fiten; Ghislain Opdenakker; Graciela Andrei (pp. a67-a68).

Silibinin (Legalon-SIL) Inhibits HCV Replication In Vitro by Isabel Najera; Vincent Leveque; Matt McCown; Julie Q. Hang; Han Ma; Sonal Rajyaguru; Amy Fung; Yanli Yang; Yang Liu; Simran Kular; Nick Cammack; Peter Ferenci; Klaus Klumpp (pp. a30).

Mutation of the Thymidine Kinases Encoded by Herpes Simplex Virus or Vaccinia Virus can Confer Resistance to 5-Iodo-4′-thio-2′-deoxyuridine by Emma Harden; Kathy Keith; Shannon Daily; Kamal Tiwari; Joseph Maddry; John Secrist; Earl Kern; Mark Prichard (pp. a48).

Therapeutic Efficacy of the Amphipathic DNA Polymer REP 9AC in the Treatment of Duck Hepatitis B Virus Infection In Vivo by Faseeha Nordeen; Arend Grosse; Jean-Marc Juteau; Andrew Vaillant; Allison Jilbert (pp. a30-a31).

Antiviral Activity of Octadecyloxypropyl Esters of 3-Hydroxy-2-(Phosphonomethoxy)Propyl Nucleosides Against Adenovirus In Vitro by J.P. Roth; T.Z. McLean; N. Valiaeva; J.R. Beadle; K.Y. Hostetler; D.L. Barnard (pp. a41-a42).

The Effect of Human Cytomegalovirus Proteins PUL97 and PUL27 on Host Interferon Responses by Rachel Gill; Etty Benveniste; Mark Prichard (pp. a47).

Notes to Authors (pp. co3).

Design, Synthesis and SAR of New Potent HIV-1 RT Inhibitors by Alba Chimirri; Erik De clercq; Giovanni Maga; Patrizia Logoteta; Stefania Ferro; Laura De Luca; Nunzio Iraci; Christophe Pannecouque; Annamaria Monforte (pp. a56-a57).

Effects of Anti-human Papillomavirus (HPV) Disease Agents on HPV Episome Levels In Vitro: Cidofovir, Podophyllotoxin, and Pyrrole–Imidazole Polyamides by Terri Edwards; Kevin Koeller; James Bashkin; Chris Fisher (pp. a68).

Formulation of Compounds for Vaginal and Rectal Delivery by Patrick Kiser Ph.D. (pp. a73).

Administration of a HepDirect™ Prodrug of 2′- C-methylcytidine to Hepatitis C Virus Infected Chimpanzees by Steven Carroll; Kenneth Koeplinger; Marissa Vavrek; Laurence Handt; Malcolm MacCoss; Scott Hecker; David Olsen (pp. a22).

The Twenty-Second International Conference on Antiviral Research (pp. a1-a18).

Prophylactic Efficacy of Intranasally Administered HSP Nanoparticles for Treating a Lethal SARS-CoV Infection in BALB/c Mice by Dale Barnard; James Wiley; Miles Wandersee; Yohichi Kumaki; Mark Young; Trevor Douglas; Allan Harmsen (pp. a32).

Computer-aided Drug Design of Novel Anti-coxsackievirus B3 Nancy Agents by Means of Hit QSAR by E. Muratov; E. Varlamova; V. Kuz’min (pp. a61).

Structure–Activity Relationship of a Novel Class of Aglycoristocetin Derivatives with Potent and Broad Activity Against Influenza Viruses by Lieve Naesens; Evelien Vanderlinden; Erzsébet Rőth; József Jekő; Graciela Andrei; Robert Snoeck; Christophe Pannecouque; Eszter Illyés; Gyula Batta; Pál Herczegh; Ferenc Sztaricskai (pp. a34-a35).

High Throughput Screening of Protease Inhibitor Libraries Using a Novel Dual Pseudotype-Based Assay for SARS-CoV Entry by Yanchen Zhou; Kai Lu; Juliet Agudelo; Graham Simmons (pp. a37-a38).

Protective Effect of a Fungal Superoxide Dismutase, Combined with a Plant Polyphenol Extract and Rimantadine Hydrochloride in the Murine Experimental Influenza Virus Infection by Julia Serkedjieva; Maria Angelova (pp. a36).

Small-molecule CCR5 Ligands that may Spare the CCR5 Function: Opportunity for New Antiviral Discovery? by Wieslaw Kazmierski; Vanessa Muniz-Medina; Susan Danehower; Stacey Jones; Terry Kenakin (pp. a43).

Synthesis and Properties of CycloSal-phosphatetriesters of Fluorescent Bicyclic Nucleoside Analogues (BCNAS) by Florian Pertenbreiter; Chris Meier (pp. a62).

Novel HCV Replication Mouse Model Using Human Hepatocellular Carcinoma Xenografts by Carl Guévin; Alain Lamarre; Patrick Labonté (pp. a28).

Synthesis and Biological Studies of Mutagenic Ribonucleoside Analogues as Potential Inducers of Error Catastrophe of Riboviruses by María-José Camarasa; Ana San-Félix; M. Teresa Peromingo; Mercedes Dávila; Ana I. de Avila; Rubén Agudo; Esteban Domingo (pp. a54).

Role of NA mutations Conferring Resistance to NA Inhibitors on Viral Fitness and Pathogenicity in A/Turkey/15/06 (H5N1) Influenza Virus by Natalia A. Ilyushina; Jon P. Seiler; Robert G. Webster; Elena A. Govorkova (pp. a71).

Evaluation of the Anti-HIV Activity of Natalizumab—An Antibody Against Integrin alpha4 by Ester Ballana; Eduardo Pauls; Gemma Moncunill; Margarida Bofill; Bonaventura Clotet; Cristina Ramo-Tello; José A. Esté (pp. a23).

New Targets within Hepatitis C Virus NS4B by Jeffrey Glenn Ph.D. (pp. a19).

Synthesis and Biological Evaluation of Acyclic Nucleotide Analogues of Bicyclic Pyrimidine Bases by Zlatko Janeba; Antonín Holý; Robert Snoeck; Graciela Andrei; Eric De Clercq; Jan Balzarini (pp. a58-a59).

Development of Microbicides with Broad Based Anti-Infective Action by Betsy Herold M.D. (pp. a73).

Indole Derivatives Are Potent Inhibitors of HIV Integrase by Periyasamy Selvam; Kasthuraiah Maddali; Yves Pommier (pp. a42).

Synthesis and Antiviral Activity of Substituted Uracils by Alexander Ivanov; Vera Tunitskaya; Olga Smirnova; Robert Buckheit; Katherine Seley-Radtke; Alexander Ozerov; Mikhail Novikov (pp. a58).

In vitro Anti-hepatitis C Virus (HCV) Activities and Resistance Profile of Debio 025, A Non-immunosuppressive Cyclophilin Binding Molecule by Lotte Coelmont; Philippe Gallay; Michael Bobardt; Suzanne Kaptein; Jan Paeshuyse; Inge Vliegen; Grégoire Vuagniaux; Johan Neyts (pp. a20).

A New Series of Tricyclic Nucleosides as Potent Inhibitors of Hepatitis C Virus RNA Replication: Design, Synthesis and Structure–Activity Relationships by Jesse Keicher; Natalia Dyatkina; Xiaoling Zheng; Vivek Rajwanshi; Marija Prhavc; Samantha Koo-McCoy; Kevin Fung; Derek Latour; Mohan Sivaraja; Uli Schmitz; Christopher Roberts; Ronald Griffith (pp. a29).

Identification and Mechanistic Studies on a Novel Class of Influenza Virus Fusion Inhibitors by Evelien Vanderlinden; Nesrin Cesur; Zafer Cesur; Fusun Goktas; Mathy Froeyen; Charles Russell; Lieve Naesens (pp. a70).

In Silico Screening for Anti-HIV-1 Compounds Targeting to Human Cyclin T1 by Takayuki Hamasaki; Masanori Baba (pp. a24).

A Mass Spectrometry-based Method to Detect Antiviral Drug Resistance in Human Cytomegalovirus by Clara Posthuma; Martha Van der Beek; Caroline Van der Blij; Willy Spaan; Louis Kroes; Eric Snijder (pp. a51).

Recruitment of the TSG101/ESCRT-I Machinery in Host Cells by Influenza Virus: Implications for Broad-Spectrum Therapy by Leyla Diaz; Josephine Cassella; Aurelio Bonavia; Roxanne Duan; David Santos; Zena Fesseha; Michael Goldblatt; Michael Kinch (pp. a71).

Editorial Board (pp. ii).

The Hepatitis C Virus NS5A: New Functions and New Mysteries by Tim Tellinghuisen Ph.D. (pp. a19).

Design, Synthesis, and Biological Evaluation of Novel Fluoro Derivatives of BCNA by Marco Derudas; Maurizio Quintiliani; Christopher McGuigan; Andrea Brancale; Geoffrey Henson; Jan Balzarini (pp. a57).

Synergistic Inhibition of Bovine Leukemia Virus Replication In Vitro by Ribavirin and alpha-Interferon by Jeffrey Isaacson; Charles Wood; Jay Reddy (pp. a24-a25).

Pyrazine Derivative Treatment of Phleboviral Infection in Cell Culture and Rodent Model Systems by Brian Gowen; MIn-Hui Wong; Kie-Hoon Jung; Donald Smee; John Morrey; Yousuke Furuta (pp. a39).

Study of Anti-Epstein–Barr virus activity of novel fluorinated heterocyclic nucleoside analogues by N. Nesterova; Yu. Shermolovich; S. Zagorodnya; A. Golovan; O. Kanishchev; G. Baranova (pp. a49).

A Study of the Safety and Pharmacokinetics of Multiple Ascending Doses of FV-100 in Healthy Subjects by Mark Matson; Helen Pentikis; Brian Boehlecke; Eric Wenzel; Geoff Henson; Amy Morris (pp. a49).

Preclinical Pharmacokinetic, Toxicokinetic and Toxicology Results for Cyclopropavir, a Promising New Agent for the Treatment of Beta- and Gamma-herpesviruses by Terry Bowlin; Jennifer Brooks; Jiri Zemlicka (pp. a46-a47).

Synthesis of CADA Analog Prodrugs Designed as Novel Down-modulators of the CD4 Receptor by Emily Scarbrough; Sreenivasa Anugu; Kurt Vermeire; Dominique Schols; Thomas Bell (pp. a63).

The Application of Phosphoramidate Protide Technology to Acyclovir confers Novel Anti-HIV Inhibition by Marco Derudas; Christopher McGuigan; Andrea Brancale; Leonid Margolis; Jan Balzarini (pp. a57).

Inhibition of Hepatitis B Virus Replication by a Set of Small Interferon-stimulated Genes by Haitao Guo; Jessica Levy; Dong Jiang; Ju-Tao Guo; Timothy Block (pp. a22).

Antiviral Activities of Nucleoside Analogs Against HSV-1 Replication in 143B Cells Expressing the Viral TK Genes with Different Initiation Codon Sites by Chong-Kyo Lee; Ju Ryung Nam; Myung-Jin Lee; Hae Soo Kim (pp. a48).

Toward Unsymmetrical CADA Analogs as Novel Down-modulators of the CD4 Receptor by Violeta Demillo; Sreenivasa Anugu; Kurt Vermeire; Dominique Schols; Thomas Bell (pp. a43-a44).

Microbicide Product Development: What Is A Microbicide? by Jim Turpin Ph.D. (pp. a73).

A High-content Screening Approach to Identify Compounds that Interfere with the Formation of the Hepatitis C Virus Replication Complex by J.M. Berke; D. Fenistein; F. Pauwels; O. Lenz; T.-I. Lin; E. Krausz; G. Fanning (pp. a27-a28).

Antiadenoviral Activity of 6-Azanucleoside Analogues by Lidiya Nosach; Olga Povnitsa; Inna Alexeeva; Larisa Palchikovska; Nadezhda Nesterova (pp. a41).

Anti-Picornavirus Activity and Other Antiviral Activity of Sulfated Exopolysaccharide from the Marine Microalga Gyrodinium impudicum Strain KG03 by Chong-Kyo Lee; Hae Soo Kim; Ju Ryung Nam; Myung-Jin Lee; Joung-Han Yim; Hong Kum Lee; Erik De Clercq (pp. a40).

Antiviral Activity of New Derivatives of Cage Compounds by Yuri Klimochkin; Vitalij Osyanin; Pavel Krasnikov; Marina Leonova; Eugene Golovin; Sergey Balakhnin; Eugene Belanov (pp. a60).

Anti-H5N1 Influenza Virus Activity of Carbocyclic Cytosine Nucleosides by J.R. Rao; A.K. Jha; A. Sharon; C.W. Day; D.L. Bernard; D.F. Smee; C.K. Chu (pp. a62-a63).

Multivalent Synthetic Lectin Polymers Against HIV by Julie Jay; Bonnie Lai; Patrick Kiser (pp. a63-a64).

Anti-influenza Efficacy of Combination Apply of Proteolytic Inhibitor E-aminocaproic Acid with Neuraminidase Inhibitor Tamiflu by V. Lozitsky; A. Frolov; A. Fedchuk; T. Grydina; L. Mudrik; L. Shitikova; L. Socheslo; V. Zadorozhnaya (pp. a34).

Invitation to the Twenty-Third International Conference on Antiviral Research, San Francisco, USA, 25–28th April, 2010 (pp. a82).

Antiviral Activity of Unithiolum Against the Human Immunodeficiency Virus and Herpes Simplex Virus by Alla Fedchuk; Victor Lozitsky; Tatyana Gridina; Svetlana Rybalko; Dasha Fedorchenko; Olga Maximenok; Felix Ershov; Olga Shcheglovitova (pp. a23).

Induction of Interferon Gamma Inducible Protein 10 by SARS-CoV Infection, Interferon Alfacon 1 and Interferon Inducer in Human Bronchial Epithelial Calu-3 Cells and BALB/c Mice by Yohichi Kumaki; Craig W. Day; Miles K. Wandersee; Jason R. Madsen; John D. Woolcott; Justin D. Hoopes; Kevin W. Bailey; Min-Hui Wong; Donald F. Smee; John D. Morrey; Dale L. Barnard (pp. a34).

Inhibition of Herpes Simplex Virus by Polyamines by Ira Yudovin-Farber; Irina Gurt; Ronen Hope; Abraham J. Domb; Ehud Katz (pp. a53).

Synthesis and SAR of 9-Arylpurines as Novel Inhibitors of Enterovirus Replication by Leire Aguado; Hendrik Jan Thibaut; María-José Camarasa; Johan Neyts; María-Jesús Pérez-Pérez (pp. a55).

Development of a Long Lasting Combination Microbicide Product Consisting of Highly Potent Compounds Exhibiting Multiple Mechanisms of Action by Karen Watson; Lu Yang; Kathleen Powers; Joseph Kurczewski; Tracy Hartman; Robert Buckheit Jr. (pp. a67).

FGI-104: A Broad-Spectrum Small Molecule Inhibitor of Viral Infection by Michael Kinch; Abdul Yunus; Hanwen Mao; Calli Lear; Guangxiang Luo; Michael Murray; Zhuhui Huang; Zena Fesseha; Hanson Chen; Gene Olinger; Michael Goldblatt (pp. a39-a40).

A Role for Nitazoxanide in Combination with STAT-C Agents for Inhibition of HCV Replication and the Potential for the Prevention of Viral Resistance by Brent Korba; Jeffery Glenn; Menashe Elazar; Jean-François Rossignol (pp. a20).

Antiproliferative Effects of Octadecyloxyethyl-Phosphonomethoxyethylguanine (ODE-PMEG) on the Growth of Human Papilloma Virus Positive Cervical Carcinoma (ME-180) Cells In Vitro and Solid Tumors in Athymic Nude Mice by Julissa Trahan; Kathy Aldern; Karl Hostetler (pp. a42).

Discovery of New Inhibitors of the Influenza H5N1 Virus by William Severson; Xi Chen; Joseph Maddry; Yong-Kyu Chu; Colleen Jonsson; Alexis McBrayer; Ronald Tapp; Donald Smee; Clinton Maddox; Subramaniam Ananthan; James Noah; Leland Black; Blake Moore; Melinda Sosa; Lucile White; Lynn Rasmussen (pp. a36-a37).

Phosphoramidate Protides Greatly Enhance the Anti-HCV Activity of 2′-Methylguanosine by Karolina Madela; Plinio Perrone; Arnaud Gilles; Johan Neyts; Chris McGuigan (pp. a29-a30).

Animal models for the study of influenza pathogenesis and therapy by Dale L. Barnard (pp. a110-a122).

Influenza A viruses causes a variety of illnesses in humans. The most common infection, seasonal influenza, is usually a mild, self-limited febrile syndrome, but it can be more severe in infants, the elderly, and immunodeficient persons, in whom it can progress to severe viral pneumonitis or be complicated by bacterial superinfection, leading to pneumonia and sepsis. Seasonal influenza also occasionally results in neurologic complications. Rarely, viruses that have spread from wild birds to domestic poultry can infect humans; such “avian influenza” can range in severity from mild conjunctivitis through the rapidly lethal disease seen in persons infected with the H5N1 virus that first emerged in Hong Kong in 1997. To develop effective therapies for this wide range of diseases, it is essential to have laboratory animal models that replicate the major features of illness in humans. This review describes models currently in use for elucidating influenza pathogenesis and evaluating new therapeutic agents.

Keywords: Influenza; Influenza virus; H5N1 avian influenza; Animal models; Mouse models; Ferret models; Antiviral therapy

Discovery and In vitro Characterization of a Novel, Chain-terminating Tricyclic Nucleoside, GL60630, with Potent Anti-HCV Activity by Christopher Roberts; Jesse Keicher; Samantha Koo-McCoy; Derek Latour; Jeffrey Pouliot; Kevin Fung; John Zhang; Mohan Sivaraja; Mark Cunningham; Jill Bechtel; Lillian Lou; Natalia Dyatkina; Ting Wang; Wenbao Li; Amy K. Patick; Ronald Griffith (pp. a20).

Nonoxynol-9 (N-9), After Repeated Applications, Does not Result in Cumulative Damage to the Murine Cervicovaginal Epithelium by Karissa Lozenski; Tina Kish-Catalone; Brian Wigdahl; Fred Krebs (pp. a64-a65).

Design, Synthesis and Anti-HIV-1 Evaluation of Novel Arylazolylthioacetanilides as Potent NNRTIS by Xinyong Liu; Peng Zhan; Christophe Pannecouque; Erik De Clercq (pp. a44-a45).

Highly Potent and Dual-acting Pyrimidinedione Inhibitors of HIV-1 Possess a High Genetic Barrier to Resistance by Robert Buckheit; Karen Watson; Tracy Hartman; Lu Yang (pp. a44).

Activation of Cyclopropavir Involves Unique Phosphorylation by Guanylate Kinase by Brian G. Gentry; Chengwei Li; John C. Drach; Jiri Zemlicka (pp. a69).

Antiflogistics as Viral Inhibitors by Georgy Danilenko; Svitlana Rybalko; Tatiana Bukhtiarova; Valentina Danilenko; Svitlana Guzhova; Victor Lozitsky (pp. a54-a55).

Oseltamivir-resistant Subpopulations of H5N1 Influenza Variants are Genetically Stable and Virulent in Ferrets by Elena A. Govorkova; Natalia A. Ilyushina; Jennifer L. McClaren; Robert G. Webster (pp. a33).

dUY11, A Rigid Amphipathic Fusion Inhibitor, Inhibits HCV Infectivity by Modulating Membrane Curvature by M. St. Vincent; A. Ustinov; N. Barsby; M. Joyce; L. Tyrrell; R. Epand; R. Epand; V. Korshun; L. Schang (pp. a21).

Antiviral Effect of a Novel Inhibitor of Influenza Virus Hemagglutinin on Influenza A (H5N1) Virus by Svetlana Rak; Elena Goncharova; Alexander Chinarev; Alexander Tuzikov; Nicolai Bovin; Alexander Ryzhikov (pp. a35-a36).

Arenaviral Inhibitory Activity of MY-24, a Novel Aristeromycin Derivative by Brain Gowen; Kie-Hoon Jung; Wei Ye; Min-Hui Wang; Deanna Larson; Donald Smee; John Morrey; Stewart Schneller (pp. a39).

Human Immunodeficiency Virus Type 1 Does Not Escape From Novel Single-Stranded DNAzyme Expression-Mediated Inhibition by Yuichiro Habu; Ryuichi Sugiyama; Hiroshi Takaku (pp. a24).

A Macromolecular Basis for Microbicides Dual Protecting Against HIV and Cytomegalovirus Infection by A. Serbin; E. Karaseva; Y. Egorov; I. Dunaeva; M. Pavlova; A. Kushch (pp. a66).

Antiviral Activity of Geneticin Against Dengue Virus by Xianchao Zhang; Peter Mason; Edward Dubovi; Alex Birk (pp. a42).

Rimantadine and Oseltamivir Combination Effects in a Therapeutic Course of Application Against Influenza A (H3N2) in Mice by Lora Simeonova; Galina Gegova; Angel S. Galabov (pp. a37).

SEVI and Semen Impair the Anti-HIV-1 Activity of Drugs and Microbicides by Kim Kyeong-Ae; Shibo Jiang; Frank Kirchhoff; Jan Muench (pp. a64).

Combination of Neuraminidase Inhibitors with T-705 for Treating Influenza Virus Infections in Cell Culture and in Mice by Donald Smee; Min-Hui Wong; Kevin Bailey; John Morrey; Masako Maekawa; Kazumi Takahashi; Yousuke Furuta (pp. a37).

Development of Hexadecyloxypropyl Tenofovir (CMX157) for HIV: Potential for Use as a Microbicide and Therapeutic by Randall Lanier; Bernhard Lampert; Lawrence Trost; Merrick Almond; George Painter (pp. a43).

Compounds Designed to Bind Conserved Regions of Human Papillomavirus (HPV) DNA show Broad-spectrum Activity Against High-risk Genotypes by James Bashkin; Terri Edwards; Kevin Koeller; Terri Edwards; Urszula Slomczynska; Chris Fisher (pp. a54).

Novel 9-Arylpurines, as Selective Inhibitors of In Vitro Enterovirus Replication by Hendrik Jan Thibaut; Leire Aguado; Lonneke van der Linden; Armando De Palma; María-José Camarasa; Jan Balzarini; Frank Van Kuppeveld; María Jesús Pérez-Pérez; Johan Neyts (pp. a73).

Drug Resistance Mutations in HSV-1 UL5 Selected using a Helicase–Primase Inhibitor: Frequency and Effects on Virus Growth and Pathogenicity by Subhajit Biswas; Soumi Sukla; Hugh J. Field (pp. a68-a69).

HCV and the Immune Response by Stan Lemon Ph.D. (pp. a19).

Synthesis, Antiviral Activity, and Cytotoxicity of Some Novel 2-Phenyl-3-disubstituted Quinazolin-4(3H)-ones by Periyasamy Selvam; Julie M. Breitenbach; Katherine Z. Borysko; John C. Drach (pp. a55).

Induction of HIV-1 Gene Expression in Human Monocytic Cells by the Failed Microbicide Carrageenan Occurs Through Activation of Toll-like Receptor 4 (TLR4) by Shawn Keogan; Vanessa Pirrone; Shendra Passic; Brian Wigdahl; Fred Krebs (pp. a64).

Use of the BelloCell System to Determine the Optimal Dose of Ribavirin to Inhibit the Expression of an HCV Replicon in 2209-23 Cells by James McSharry; Diane Singer; Robert Kulawy; Ashley Brown; George Drusano (pp. a30).

A Novel Small-molecule CCR5 Agonist, ESN-196, with Potent R5 HIV-1 Activity by Thierry Ferain; Dominique Schols; Jérôme Bernard; Graeme Fraser (pp. a23-a24).

CXCR4 Antagonists: A New Generation of Configurationally Restricted Bis-azamacrocyclic Compounds by Abid Khan; Gary Nicholson; Graeme McRobbie; John Greenman; Christophe Pannecouque; Dirk Daelemans; Dominique Schols; Erik De CLercq; Timothy J. Hubin; Stephen J. Archibald (pp. a59-a60).

Design, Molecular Modelling Studies of Specific Targeted Candidate Inhibitors of HCV NS5B RNA Polymerase by P. Selvam; M. Chandramohan; J. Pranitha; N. Saravanan Prabhu; Muthuvels Suresh kumar (pp. a31-a32).

Macrocyclic Polyamines Targeting the Cellular HIV Co-receptors, CXCR4 and CCR5 by Sunil Hamal; Li Cui; Bell Thomas; Aquaro Stefano; Dana Huskens; Dominique Schols (pp. a58).

Novel Small Molecule Inhibitors of Dengue Virus Replication by Chelsea Byrd; Jessica Page; Chris Harver; Doug Grosenbach; Aklile Berhanu; Dennis Hruby; Robert Jordan (pp. a38).

Evaluation of Octadecyloxyethyl Esters of 3-Hydroxy-2-(phosphonomethoxy)propyl Nucleosides Against HCMV, HSV and Poxviruses by Nadejda Valiaeva; Julissa Trahan; Kathy A. Keith; Caroll Hartline; Mark Prichard; James R. Beadle; Karl Y. Hostetler (pp. a52).

High-throughput In Vitro HIV Rev-multimerization Assay by Thomas Vercruysse; George Pavlakis; Dirk Daelemans (pp. a46).

A Tetrazolo-pyrimidine Induces Intracellular Redistribution of Hepatitis B Surface Antigen, Resulting in Reduced Secretion by Cally Goddard; Haitao Guo; Xiadong Xu; Wenquan Yu; Courtney Mills; Timothy Block; Andrea Cuconati (pp. a21).

Synthesis and Evaluation of Novel Acyclovir Phosphoramidates as Anti-HIV Agents by Davide Carta; Christopher McGuigan; Leonid Margolis; Jan Balzarini (pp. a56).

Resistance Developed Against Alamethicin an Antimicrobial Peptide in Enterococcus faecalis is Directly Proportional to its Concentration by Jitender Mehla; S.K. Sood (pp. a65).

Feglymycin, a Unique 13 Amino-acid Peptide, With a Novel Mechanism of Anti-HIV-1 Activity by Dominique Schols; Geoffrey Férir; Bart Hoorelbeke; Anne Hänchen; Frank Dettner; Roderich D. Süssmuth (pp. a25).

A Microbicide Perspective: Past, Present, and Future by Sharon Hillier Ph.D. (pp. a73).

New peptidomimetic prodrugs of acyclic and cyclic cidofovir: sar studies of chemical and enzymatic activation mechanisms by Charles E. McKenna; Larryn W. Peterson; Boris A. Kashemirov; Michaela Serpi; Stefanie Mitchell; Jae Seung Kim; John M. Hilfinger; John C. Drach (pp. a75).

Activity of Certain 5-Substituted-4′-Thio Pyrimindine Nucleosides against Orthopoxvirus Infections by Earl Kern; Mark Prichard; Debra Quenelle; Kathy Keith; Kamal Tiwari; Joseph Maddry; John Secrist III (pp. a72).

A Study of the Safety and Pharmacokinetics of Single and Multiple Doses of FV-100 in Subjects 65 Years and Over by Mark Matson; George Atiee; Helen Pentikis; Brian Boehlecke; Eric Wenzel; Amy Morris (pp. a49).

Assay Development for Antiviral Drug Efficacy Evaluation Against Dengue Virus by Qianjun Li (pp. a40-a41).

A Small Llama Antibody Fragment Efficiently Inhibits the HIV Rev Multimerization In Vitro by Thomas Vercruysse; Els Pardon; Jan Steyaert; Dirk Daelemans (pp. a27).

The transport of anti-HIV drugs across blood–CNS interfaces: Summary of current knowledge and recommendations for further research by Lavanya Varatharajan; Sarah A. Thomas (pp. a99-a109).

The advent of highly active antiretroviral therapy (HAART), which constitutes HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors, has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection in resource-rich countries. However, this disease still kills several million people each year. Though the reason for therapeutic failure is multi-factorial, an important concern is the treatment and control of HIV within the central nervous system (CNS). Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This not only results in virological resistance, but also is often associated with the development of complications such as HIV-associated dementia. The CNS delivery of anti-HIV drugs is limited by the blood–brain and blood–CSF interfaces due to a combination of restricted paracellular movement, powerful metabolic enzymes and numerous transporters including members of the ATP binding cassette (ABC) and solute carrier (SLC) superfamilies. A better appreciation of the transporters present at the brain barriers will prove a valuable milestone in understanding the limited brain penetration of anti-HIV drugs in HIV and also aid the development of new anti-HIV drugs and drug combinations, with enhanced efficacy in the CNS. This review aims to summarise current knowledge on the transport of anti-HIV drugs across the blood–brain barrier and the choroid plexus, as well as provide recommendations for future research.

Keywords: Abbreviations; BBB; blood–brain barrier; P-gp; P-glycoprotein; MRP; multi-drug resistance associated protein; HAART; highly active antiretroviral therapy; PIs; protease inhibitors; NRTIs; nucleoside reverse transcriptase inhibitors; NNRTIs; non-nucleoside reverse transcriptase inhibitors; NtRTIs; nucleotide reverse transcriptase inhibitors; HAD; HIV-associated dementia; HIVE; HIV encephalitis; MND; mild neurocognitive disorder; MDR-1; multi-drug resistance gene 1; BCRP; breast cancer resistance protein; OAT; organic anion transporter; OATP; organic anion-transporting polypeptide; CSF; cerebrospinal fluid; CNS; central nervous system; AIDS; acquired immunodeficiency syndrome; HAD; HIV-associated dementia; ABC; ATP binding cassette; SLC; solute carrier superfamily; ddI; 2′,3′-dideoxyinosine; ddC; 2′3′-dideoxycytidine; 3TC; (−)-2′-deoxy-3′-thiacytidine; AZT; zidovudine; ENT; equilibrative nucleoside transporter; CNT; concentrative nucleoside transporter; ET-1; endothelin-1; LPS; lipopolysaccharideBlood–brain barrier; Choroid plexus; HIV; HAART; Transporters; P-Glycoprotein; Antiretroviral drugs

The Activity of New Cage Compounds Against Avian Influenza Virus (H5N1) by Evgeny Belanov; Marina Leonova; Vladimir Osyanin; Pavel Krasnikov; Sergey Kuznetsov; Andrey Shiraev; Evgeny Golovin; Olga Serova; Nikolay Bormotov; Sergei Balakhnin; Yurii Klimochkin (pp. a32-a33).

CXCR4 Chemokine Receptor Antagonists from Ultra-rigid Metal Complexes Profoundly Inhibit HIV-1 Replication, and also AMD3100-resistant Strains by Stephen J. Archibald; Dirk Daelemans; Timothy J. Hubin; Dana Huskens; Dominique Schols; Kristel Van Laethem; Erik De Clercq; Christophe Pannecouque (pp. a45).

Predicted Models of Resistance and Hypersensitivity Conferred by Natural Polymorphisms of HIV-1 Integrase by Raymond Hewer; Telisha Traut; Judy Coates; Bradley Williams (pp. a24).

Sections

Personal tools

Antiviral Research (v.82, #2)

Sections

Personal tools

Local resources

Antiviral Research (v.82, #2)