# ANTIVIRAL DRUGS AND EPSTEIN-BARR VIRUS INFECTION STATES

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1991 · $176,431

## Abstract

Building on our previous work with antiviral drugs active against
EBV we propose six specific aims to address fundamental issues
posed by EBV infection: productive and persistent infection,
latency, drug resistance, reversibility of drug effect, and cellular
transformation.  The first and third aims are designed to coupled
investigation of new drugs or drug combinations with EBV biologic
systems.  Synergistic combinations (aim 2) of drugs with different
modes of action may offer an approach to combat drug-
resistance, reversibility and reduce cytotoxicity.  The second aim
deals with the mode of action of the drugs in general and AZT in
particular.  Based on what we have learned from our studies with
ACV, DHPG, BVdU, FMAU and FIAC we will investigate (a) drug
phosphorylation, (b) role of EBV TK, (c) interaction of EBV
polymerase with drug-triphosphates, (d) chain termination, (e)
drug incorporation, (f) reversibility, (g) role of thymidylate kinase,
and (h) drug-binding domains.  In the fourth aim we will use
mutated EBV polymerase-expressing cell lines generated by site-
directed mutagenesis to study cross-resistance to the new drugs.
In the fifth aim we present a plan to disrupt or cure EBV episomal
maintenance with synthetic EBNA-1 antisense methylated
oligonucleotides by blocking synthesis of EBNA-1 protein needed
for binding to the EBV ori-P.  The final aim deals with blocking
EBV-induced transformation by selected new drugs and interferon
alpha and gamma, coupled with use of EBNA-1 antisense
oligonucleotides to reduce episomal numbers during
transformation.  Data obtained from these studies will facilitate
understanding of mechanisms of drug action, help in the
development of selective antiviral agents, and open new
approaches to dealing with EBV infection.

## Key facts

- **NIH application ID:** 3127028
- **Project number:** 5R01AI017205-12
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** JOSEPH S PAGANO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $176,431
- **Award type:** 5
- **Project period:** 1980-08-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127028

## Citation

> US National Institutes of Health, RePORTER application 3127028, ANTIVIRAL DRUGS AND EPSTEIN-BARR VIRUS INFECTION STATES (5R01AI017205-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127028. Licensed CC0.

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