Cascade search for HSV-1 combinatorial drugs with high antiviral efficacy and low toxicity

Effect of Azone upon the in vivo antiviral efficacy of cidofovir or acyclovir topical formulations in treatment/prevention of cutaneous HSV-1 infections and its correlation with skin target site free drug concentration in hairless mice

International Journal of Pharmaceutics ◽

10.1016/s0378-5173(02)00705-6 ◽

2003 ◽

Vol 253 (1-2) ◽

pp. 159-168 ◽

Cited By ~ 19

Author(s):

Mohsen I Afouna ◽

Timothy K Fincher ◽

Abdel-Azim A Zaghloul ◽

Indra K Reddy

Keyword(s):

Drug Concentration ◽

Free Drug ◽

Target Site ◽

Free Drug Concentration ◽

Hairless Mice ◽

Topical Formulations ◽

Antiviral Efficacy ◽

Hsv 1

Download Full-text

The Antiherpesvirus Activity of H2G [(R)-9-[4-Hydroxy-2-(Hydroxymethyl)Butyl]Guanine] Is Markedly Enhanced by the Novel Immunosuppressive Agent Mycophenolate Mofetil

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.12.3285 ◽

1998 ◽

Vol 42 (12) ◽

pp. 3285-3289 ◽

Cited By ~ 25

Author(s):

Johan Neyts ◽

Graciela Andrei ◽

Erik De Clercq

Keyword(s):

Mycophenolate Mofetil ◽

Parent Compound ◽

Immunosuppressive Agent ◽

The Novel ◽

Kidney Transplant Recipients ◽

Imp Dehydrogenase ◽

Varicella Zoster ◽

Antiviral Efficacy ◽

Simplex Virus ◽

Hsv 1

ABSTRACT Mycophenolate mofetil (MMF) has been approved as an immunosuppressive agent in kidney transplant recipients and may thus be used concomitantly with antiherpetic agents, which are used for the treatment of intercurrent herpesvirus infections. We have recently demonstrated that MMF and its parent compound mycophenolic acid (MPA), which is a potent inhibitor of IMP dehydrogenase, potentiate the antiherpesvirus activity of acyclovir, ganciclovir, and penciclovir. We have now evaluated the antiviral efficacy of the combination of MPA and the novel antiherpesvirus agent H2G [(R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine]. When combined with H2G, MPA (at concentrations ranging from 0.25 to 10 μg/ml, which are readily attainable in human plasma) markedly potentiated the antiviral efficacy of H2G against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as reflected by a 10- to 150-fold decrease in the 50% effective concentration. Moreover, the activity of H2G against a thymidine kinase-deficient strain of HSV-1 (TK− HSV-1) was increased more than 2,500-fold when combined with MPA. MPA by itself had little or no effect on the replication of these viruses. Similar observations were made for varicella-zoster virus. Also, ribavirin (another inhibitor of IMP dehydrogenase) caused a marked enhancement of the activity of H2G against HSV-1 (10-fold), HSV-2 (10-fold), and TK− HSV-1 (>185-fold). Exogenously added guanosine reversed the potentiating effects of MPA on the antiviral activity of H2G, indicating that this potentiating effect resulted from a depletion of the endogenous dGTP pools, thus favoring the inhibitory action of the H2G triphosphate on the viral DNA polymerase.

Download Full-text

In Vivo Antiviral Efficacy of a Dipeptide Acyclovir Prodrug, Val-Val-Acyclovir, against HSV-1 Epithelial and Stromal Keratitis in the Rabbit Eye Model

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.02-1251 ◽

2003 ◽

Vol 44 (6) ◽

pp. 2529 ◽

Cited By ~ 32

Author(s):

Banmeet S. Anand ◽

James M. Hill ◽

Surajit Dey ◽

Koichi Maruyama ◽

Partha S. Bhattacharjee ◽

...

Keyword(s):

Eye Model ◽

Rabbit Eye ◽

Antiviral Efficacy ◽

Stromal Keratitis ◽

Hsv 1

Download Full-text

Antiviral efficacy of Limonium densiflorum against HSV-1 and influenza viruses

South African Journal of Botany ◽

10.1016/j.sajb.2014.02.003 ◽

2014 ◽

Vol 92 ◽

pp. 65-72 ◽

Cited By ~ 12

Author(s):

Faten Medini ◽

Jean Legault ◽

André Pichette ◽

Chedly Abdelly ◽

Riadh Ksouri

Keyword(s):

Influenza Viruses ◽

Antiviral Efficacy ◽

Hsv 1

Download Full-text

The relative antiviral efficacy of twice daily cidofovir versus acyclovir and trifluridine in the HSV-1/NZ rabbit keratitis model

Antiviral Research ◽

10.1016/s0166-3542(97)83282-2 ◽

1997 ◽

Vol 34 (2) ◽

pp. A82

Keyword(s):

Antiviral Efficacy ◽

Hsv 1

Download Full-text

Effect of Complexes of Cobalt With Aminoacids on the Replication of Herpes Simplex Virus Type 1 (HSV-1)

Metal-Based Drugs ◽

10.1155/mbd.1996.149 ◽

1996 ◽

Vol 3 (3) ◽

pp. 149-154 ◽

Cited By ~ 1

Author(s):

T. Varadinova ◽

S. Shishkov ◽

M. Panteva ◽

P. Bontchev

Keyword(s):

The Body ◽

Target Cells ◽

Stability Structure ◽

Charge Stability ◽

Low Toxicity ◽

Virucidal Effect ◽

Simplex Virus ◽

Hsv 1

Cobalt, being essential metal, influences different physiological and enzymatic functions. As cobalt does not accumulate in the body, Co-compounds have relatively low toxicity. The aim of the present study is the effect of complexes of Co(II) with aminoacids - lysine, arginine, histidine and serine on HSV-1 replication. No effect of [O2Co(his)4].nH2O and [O2Co(arg)2].nH2O on HSV-1 infection in vitro was found. Both, [O2Co(lys)2].nH2O and [O2Co(ser)2].nH2O suppress the attachement of HSV-1 particles onto target cells and the viral replication as well. Moreover, the properties of the particular Co-complex (charge, stability, structure) are manifestated by their virucidal effect. Thus, [O2Co(ser)2].nH2O irreversibly inhibits the infectious activity of free HSV-1 virions, while virucidal effect of [O2Co(lys)2].nH2O is completely reversible after the 2h of contact.

Download Full-text

Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3-D structure of recombinant capsid

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140579 ◽

1995 ◽

Vol 53 ◽

pp. 840-841

Author(s):

Z. Hong Zhou ◽

Jing He ◽

Joanita Jakana ◽

J. D. Tatman ◽

Frazer J. Rixon ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

3D Structure ◽

Structure Study ◽

Herpes Simplex Virus 1 ◽

Shell Proteins ◽

Life Threatening ◽

Infected Cells ◽

Simplex Virus ◽

Hsv 1

Herpes simplex virus-1 (HSV-1) is a ubiquitous virus which is implicated in diseases ranging from self-curing cold sores to life-threatening infections. The 2500 Å diameter herpes virion is composed of a glycoprotein spike containing, lipid envelope, enclosing a protein layer (the tegument) in which is embedded the capsid (which contains the dsDNA genome). The B-, and A- and C-capsids, representing different morphogenetic stages in HSV-1 infected cells, are composed of 7, and 5 structural proteins respectively. The three capsid types are organized in similar T=16 icosahedral shells with 12 pentons, 150 hexons, and 320 connecting triplexes. Our previous 3D structure study at 26 Å revealed domain features of all these structural components and suggested probable locations for the outer shell proteins, VP5, VP26, VP19c and VP23. VP5 makes up most of both pentons and hexons. VP26 appeared to bind to the VP5 subunit in hexon but not to that in penton.

Download Full-text