2. Academic Validation
  3. 3-Deazaguanosine inhibits SARS-CoV-2 viral replication and reduces the risk of COVID-19 pneumonia in hamster

3-Deazaguanosine inhibits SARS-CoV-2 viral replication and reduces the risk of COVID-19 pneumonia in hamster

  • iScience. 2025 Mar 1;28(4):112140. doi: 10.1016/j.isci.2025.112140.
Noriko Saito-Tarashima 1,  Takaaki Koma 2 3,  Naoto Hinotani 1,  Keigo Yoshida 1,  Moka Ogasa 1,  Akiho Murai 1,  Syuya Inoue 1,  Tomoyuki Kondo 2,  Naoya Doi 2,  Koichi Tsuneyama 3 4,  Masako Nomaguchi 2 3,  Noriaki Minakawa 1
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Science, Tokushima University, 1-78-1 Shomachi, Tokushima, Tokushima 770-8505, Japan.
  • 2 Department of Microbiology, Graduate School of Medicine, Tokushima University, 3-18-15 Kuramoto, Tokushima, Tokushima 770-8503, Japan.
  • 3 Department of PostLED Photonics Research, Institute of PostLED Photonics, Tokushima University, 2-1 Minamijosanjima, Tokushima, Tokushima 770-8506, Japan.
  • 4 Department of Pathology and Laboratory Medicine, Graduate School of Medicine, Tokushima University, 3-18-15 Kuramoto, Tokushima, Tokushima 770-8503, Japan.
PMID: 40171487 DOI: 10.1016/j.isci.2025.112140
Abstract

The COVID-19 pandemic highlighted the serious threat that coronaviruses have on public health. Because coronavirus continuously undergoes cross-species transmission, additional therapeutic agents and targets are urgently needed. Here, we show that a 3-deazapurine ribonucleoside, 3-Deazaguanosine (C3Guo, 2), has potent Antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unexpectedly, C3Guo (2) does not act as an inhibitor of RNA-dependent RNA polymerase (RdRp), which is the therapeutic target of two key nucleoside/nucleotide inhibitors approved for the treatment of COVID-19 (Remdesivir and Molnupiravir); instead, it seems to function by targeting the capping machinery of viral RNA. In hamsters infected with SARS-CoV-2, administration of 2 markedly reduced infectious viral titers, and prevented the development of COVID-19 pneumonia better than Molnupiravir. The potency of 2 against SARS-CoV-2 underscores its potential as an effective therapeutic agent for COVID-19 and future zoonotic coronavirus infections and raises the possibility of Antiviral nucleoside analogs with alternative therapeutic targets to RdRp.

Keywords

Biological sciences; Health sciences; Immunology.

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