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Discovery of a small-molecule inhibitor of KSHV lytic replication from the MMV pandemic response box.
Okpara, Michael O; Weaver, Frederick; Whitehouse, Adrian; Veale, Clinton G L; Edkins, Adrienne L.
Afiliação
  • Okpara MO; Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa.
  • Weaver F; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
  • Whitehouse A; Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK; Astbury Centre for Structural Molecular Biolo
  • Veale CGL; Department of Chemistry, University of Cape Town, Rondebosch, Cape Town, South Africa.
  • Edkins AL; Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa; Centre for Chemico- and Biomedicinal Research (CCBR), Rhodes University, Grahamstown, South Africa. Electronic address: a.edkins@ru.ac.za.
Antiviral Res ; 230: 105990, 2024 Aug 16.
Article em En | MEDLINE | ID: mdl-39154751
ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS). KSHV is one of the oncoviruses that contribute to 1.5 million new infection-related cancer cases annually. Currently, there are no targeted therapies for KSHV-associated diseases. Through the development of a medium-throughput phenotype-based ELISA screening platform based on KSHV ORF57 protein detection, we screened the Medicines for Malaria Venture (MMV) Pandemic Response Box for non-cytotoxic inhibitors of KSHV lytic replication. MMV1645152 was identified as a promising inhibitor of KSHV lytic replication, suppressing KSHV immediate-early and late lytic gene expression and blocking the production of infectious KSHV virion particles at non-cytotoxic concentrations in cell line models of KSHV infection with or without EBV coinfection. MMV1645152 is a promising hit compound for the development of future therapeutic agents against KSHV-associated malignancies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Antiviral Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: África do Sul

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Antiviral Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: África do Sul
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