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RNA‐dependent RNA polymerase, RdRP, a promising therapeutic target for cancer and potentially COVID‐19

  • Machitani, Mitsuhiro1
  • Yasukawa, Mami1
  • Nakashima, Jotaro1
  • Furuichi, Yasuhiro2
  • Masutomi, Kenkichi1
  • 1 National Cancer Center Research Institute, Japan , (Japan)
  • 2 GF Mille Co., Ltd., Gifu University, Japan , (Japan)
Published Article
Cancer Science
John Wiley and Sons Inc.
Publication Date
Aug 17, 2020
DOI: 10.1111/cas.14618
PMID: 32805774
PMCID: PMC7461281
PubMed Central


A recent outbreak of coronavirus disease 19 (COVID‐19) caused by the novel severe acute respiratory coronavirus 2 (SARS‐CoV‐2) has driven a global pandemic with catastrophic consequences. The rapid development of promising therapeutic strategies against COVID‐19 is keenly anticipated. Family Coronaviridae comprises positive, single‐stranded RNA viruses that use RNA‐dependent RNA polymerase (RdRP) for viral replication and transcription. Since the RdRP of viruses in this family and others plays a pivotal role in infection, it is a promising therapeutic target for developing antiviral agents against them. A critical genetic driver for many cancers is the catalytic subunit of telomerase: human telomerase reverse transcriptase (hTERT), identified initially as an RNA‐dependent DNA polymerase. However, even though hTERT is a DNA polymerase, it has phylogenetic and structural similarities to viral RdRPs. Researchers worldwide, including the authors of this review, are engaged in developing therapeutic strategies targeting hTERT. We have published a series of papers demonstrating that hTERT has RdRP activity and that this RdRP activity in hTERT is essential for tumor formation. Here, we review the enzymatic function of RdRP in virus proliferation and tumor development, reminding us of how the study of the novel coronavirus has brought us to the unexpected intersection of cancer research and RNA virus research.

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