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Titolo:
A rapid plate assay for the screening of inhibitors against herpesvirus DNA polymerases and processivity factors
Autore:
Lin, K; Ricciardi, RP;
Indirizzi:
Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Microbiol, Philadelphia, PA 19104 USA Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 & Biophys, Philadelphia, PA 19104 USA
Titolo Testata:
JOURNAL OF VIROLOGICAL METHODS
fascicolo: 2, volume: 88, anno: 2000,
pagine: 219 - 225
SICI:
0166-0934(200008)88:2<219:ARPAFT>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; ANTIVIRAL DRUGS; IN-VITRO; VIRUS; SEQUENCES; HUMAN-HERPESVIRUS-8; IDENTIFICATION; SENSITIVITY; REPLICATION;
Keywords:
herpesvirus; DNA polymerase; processivity factor; antiviral; high-throughput screening;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Ricciardi, RP Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 ladelphia, PA 19104 USA
Citazione:
K. Lin e R.P. Ricciardi, "A rapid plate assay for the screening of inhibitors against herpesvirus DNA polymerases and processivity factors", J VIROL MET, 88(2), 2000, pp. 219-225

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly identified humanpathogen with tumorigenic potential. The DNA polymerase (Pol-8) and processivity factor (PF-8) of KSHV were cloned recently. It was shown that PF-8 forms specifically a complex with Pol-8 in vitro and allows it to synthesizefully-extended DNA. Since both Pol-8 and PF-8 are apparently essential forviral DNA replication and since they cannot be substituted by any other cellular or viral proteins, they are potentially excellent antiviral targets. The development of a mechanistic plate assay is now described, which is suitable for rapid high-throughput screening of antiviral agents against Pol-8 and PF-8. The assay allows the measurement of not only total DNA synthesis activity (i.e. nucleotide incorporation) but also processivity (i.e. fully-extended DNA product). In this plate assay, any of the screen-compounds with an inhibitory effect against the total DNA synthesis activity and/or the processivity could be potential antiviral agents that target Pol-8 and/orPF-8. Particularly, since PF-8 is highly specific for Pol-8, the discoveryof inhibitory agents against PF-8 may lead to specific antiviral therapieswith minimal toxicity to host cells. This assay should be suitable for screening for inhibitory compounds against polymerases and processivity factors of other herpesviruses as well. (C) 2000 Elsevier Science B.V. All rightsreserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 20:42:00