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Updated: Dec 20, 2025
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Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV
Published on: September 14, 2010
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Pemetrexed inhibits Kaposi's sarcoma-associated herpesvirus replication through blocking dTMP synthesis
Jungang Chen1, Haiwei Zhang1, Xulin Chen2
1State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Antiviral Research
|May 29, 2020
Summary
Pemetrexed effectively inhibits Kaposi's sarcoma-associated herpesvirus (KSHV) replication by blocking essential DNA synthesis. This FDA-approved drug offers a promising new strategy against KSHV infections, potentially overcoming current treatment limitations.
Area of Science:
- Virology
- Oncology
- Pharmacology
Background:
- Kaposi's sarcoma-associated herpesvirus (KSHV) causes severe diseases, especially in immunocompromised individuals.
- Current KSHV treatments face challenges like adverse effects and drug resistance.
- Novel therapeutic strategies are needed to combat KSHV infections effectively.
Purpose of the Study:
- To identify novel anti-KSHV agents from an FDA-approved drug library.
- To characterize the antiviral mechanism of identified compounds.
- To evaluate the potential of new agents for KSHV treatment.
Main Methods:
- Screening of an FDA-approved drug library against KSHV.
- Antiviral activity assessment using IC50 determination.
- Characterization of pemetrexed's mechanism of action on viral DNA replication and dTMP synthesis.
Main Results:
- Pemetrexed identified as a potent anti-KSHV agent with IC50 of 90 nM.
- Pemetrexed inhibits KSHV lytic replication and reduces infectious virions.
- Antiviral activity is linked to the inhibition of dTMP synthesis via folate-dependent enzymes.
Conclusions:
- Pemetrexed demonstrates significant anti-KSHV activity by blocking dTMP synthesis.
- Pemetrexed exhibits broad-spectrum anti-herpesvirus potential.
- Pemetrexed is a promising candidate for developing new KSHV therapies.
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