A new compound, phomaherbarine A, induces cytolytic reactivation in epstein-barr virus-positive B cell lines

So-Eun Bae; Jin Won Choi; Ji-Woon Hong; Hyeri Ku; Kyu-Young Sim; Gwang-Hoon Ko; Dae Sik Jang; Sang Hee Shim; Sung-Gyoo Park

doi:10.1016/j.antiviral.2024.105906

A new compound, phomaherbarine A, induces cytolytic reactivation in epstein-barr virus-positive B cell lines

Antiviral Res. 2024 May 10:227:105906. doi: 10.1016/j.antiviral.2024.105906. Online ahead of print.

Authors

So-Eun Bae¹, Jin Won Choi², Ji-Woon Hong¹, Hyeri Ku², Kyu-Young Sim¹, Gwang-Hoon Ko¹, Dae Sik Jang³, Sang Hee Shim⁴, Sung-Gyoo Park⁵

Affiliations

¹ College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, 08826, Republic of Korea.
² Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
³ Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
⁴ Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address: sanghee_shim@snu.ac.kr.
⁵ College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address: riceo2@snu.ac.kr.

PMID: 38735576
DOI: 10.1016/j.antiviral.2024.105906

Abstract

Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies. The present study assessed the ability of phomaherbarine A, a novel compound derived from the endophytic fungus Phoma herbarum DBE-M1, to stimulate lytic replication of EBV in B95-8 cells. Phomaherbarine A was found to efficiently initiate the expression of both early and late EBV lytic genes in B95-8 cells, with this initiation being further heightened by the addition of phorbol myristate acetate and sodium butyrate. Moreover, phomaherbarine A demonstrated notable cytotoxicity against the EBV-associated B cell lymphoma cell lines B95-8 and Raji. Mechanistically, phomaherbarine A induces apoptosis in these cells through the activation of caspase-3/7. When combined with ganciclovir, phomaherbarine A does not interfere with the reduction of viral replication by ganciclovir and sustains its apoptosis induction. In conclusion, these findings indicate that phomaherbarine A may be a promising candidate for therapeutic intervention in patients with EBV-associated B cell lymphomas.

Keywords: Acyclovir; Cytolytic virus activation therapy; EBV-Associated B cell lymphoma; Epstein-barr virus; Ganciclovir; Tetramic acid; phomaherbarine A.