In vitro antiviral activity of distamycin A against clinical isolates of herpes simplex virus 1 and 2 from transplanted patients.
OBJECTIVE
Herpes simplex virus (HSV) infections in immunocompromised individuals may require prolonged antiviral therapy resulting in the emergence of viral strains resistant to the currently employed antiviral drugs. Distamycin A (DA), a basic antibiotic belonging to the lexitropsin DNA minor groove binding drugs, exhibits antiviral properties. In this study we evaluated the in vitro cytotoxicity and antiviral activity of DA against HSV type 1 and HSV type 2 clinical isolates from transplanted patients and compared them with those of acyclovir (ACV) in search of alternative antiviral drugs.


METHODS
Viral detection and typing was performed by multiplex PCR and immunofluorescence assay; the in vitro cytotoxicity of DA and the antiviral activity of ACV and DA was evaluated respectively by neutral red uptake assay and plaque reduction assay for HSV2 isolates and fluorescence reduction assay for HSV1 isolates.


RESULTS
Tissue culture 50% cytotoxic concentration of DA was 58 muM. Tissue culture 50% inhibitory concentration values ranged from 0.16 to 7.4 muM for the ACV-sensitive and from 5.4 to 32 muM for the ACV-resistant viral strains.


CONCLUSIONS
In spite of the lower activity against ACV-resistant strains, DA may be used as an antiherpetic drug.
Matteoli
Barbara
B
Sezione di Virologia, Dipartimento di Patologia Sperimentale B.M.I.E., Università di Pisa, Pisa, Italia.
Bernardini
Sara
S
Iuliano
Rodolfo
R
Parenti
Silvia
S
Freer
Giulia
G
Broccolo
Francesco
F
Baggiani
Angelo
A
Subissi
Alessandro
A
Arcamone
Federico
F
Ceccherini-Nelli
Luca
L
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D004214:Distamycins / Q000494:pharmacology* / Q000633:toxicity; D005453:Fluorescence; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009499:Neutral Red / Q000378:metabolism; D018139:Simplexvirus / Q000187:drug effects* / Q000302:isolation & purification; D014180:Transplantation; D014709:Vero Cells; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D004214:Distamycins; D009499:Neutral Red; C030000:stallimycin; D000212:Acyclovir