Combination of Remdesivir and Ivermectin Exerts Highly Potent and Synergistic Antiviral Activity Against Murine Coronavirus and SARS-CoV-2 Infections
et al., Cells, doi:10.3390/cells15131146, Jun 2026
In vitro study showing synergistic antiviral activity of ivermectin and remdesivir against murine coronavirus (MHV) and SARS-CoV-2.
Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury, Leo, Briciu, Muntean, Petrov, Arch show increased risk of liver injury, Negru, Cheng, Mohammed, Kwok, Zhu show increased risk of cardiac disorders, and Kwok, Merches, Akinci, Tang, Bagheri show increased risk of mitochondrial toxicity with remdesivir.
Study covers ivermectin and remdesivir.
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Lew et al., 24 Jun 2026, USA, peer-reviewed, 10 authors.
Contact: kaistan@nus.edu.sg (corresponding author), zzlew@u.nus.edu, douglastay@nus.edu.sg, miccjh@nus.edu.sg, entwdy@nus.edu.sg, jocelyn_ong_wen_xin@immunol.a-star.edu.sg, low_jing_hui@immunol.a-star.edu.sg, anand_andiappan@immunol.a-star.edu.sg, entliuj@nus.edu.sg, micctk@nus.edu.sg.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract:
Article
Combination of Remdesivir and Ivermectin Exerts Highly Potent and Synergistic Antiviral Activity Against Murine Coronavirus and SARS-CoV-2 Infections
Ryan Z. Z. Lew 1,2,3 , Douglas J. W. Tay 1,2,3 , Jocelyn W. X. Ong 4 , Jing Hui Low 4 , Jing Liu 5 , De Yun Wang 3,5 , Justin J. H. Chu 1,2,3 , Anand Kumar Andiappan 4 , Kai Sen Tan 1,2,3, * and Vincent T. K. Chow 1,3, *
- 1 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore 117545, Singapore; zzlew@u.nus.edu (R.Z.Z.L.); douglastay@nus.edu.sg (D.J.W.T.); miccjh@nus.edu.sg (J.J.H.C.)
- 2 NUS Medicine Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore 117599, Singapore
- 3 Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore 117597, Singapore; entwdy@nus.edu.sg
- 4 Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore 138648, Singapore; jocelyn\_ong\_wen\_xin@immunol.a-star.edu.sg (J.W.X.O.); low\_jing\_hui@immunol.a-star.edu.sg (J.H.L.); anand\_andiappan@immunol.a-star.edu.sg (A.K.A.)
- 5 Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore 119228, Singapore; entliuj@nus.edu.sg
* Correspondence: kaistan@nus.edu.sg (K.S.T.); micctk@nus.edu.sg (V.T.K.C.)
Abstract
The COVID-19 pandemic highlighted the urgent need to develop effective and broadspectrum antiviral therapies against coronaviruses. One strategy to address this concern is a combination therapy using repurposed drugs against zoonotic viruses with pandemic potential. We previously demonstrated that the combination of Remdesivir and Ivermectin is highly potent and synergistic in inhibiting the replication of murine hepatitis virus (MHV) in RAW264.7 macrophages. This study investigated the interactions between the drug combination, coronavirus and host by proteomics and RNA sequencing of MHV-infected H2.35 murine liver epithelial cells. Time-of-addition and time-of-removal assays suggested that the drug combination likely affected the synthesis of viral RNA and viral protein. This combination drastically diminished the live virus titer greater than the respective monotherapies in MHV-infected H2.35 cells (by ~4 log10), as well as in SARS-CoV-2-infected VeroE6 cells and human nasal epithelial cells. Proteomic and transcriptomic analyses revealed that viral protein and RNA levels were significantly depressed upon combination treatment. The drug combination exhibited considerable negative effects upon host RNA processes and resulted in the upregulation of host protein processes (e.g., response to unfolded protein; protein insertion into ER membrane). Molecular pathways affected by the combination treatment were markedly distinct from the monotherapies and indicated that Ivermectin enhances Remdesivir by modulating critical host processes to synergistically exert its inhibitory effect on the coronavirus replication cycle.
Keywords: Remdesivir; Ivermectin; combination therapy; repurposed drugs; murine hepatitis virus; SARS-CoV-2; proteomics; transcriptomics; host pathways
Academic Editor: Shih-Heng (David) Chen
Received: 4 May 2026
Revised: 10 June 2026
Accepted: 21 June 2026
Published: 24 June 2026
Copyright:
©2026 by the authors.
Licensee MDPI, Basel, Switzerland.
This..
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"abstract": "<jats:p>The COVID-19 pandemic highlighted the urgent need to develop effective and broad-spectrum antiviral therapies against coronaviruses. One strategy to address this concern is a combination therapy using repurposed drugs against zoonotic viruses with pandemic potential. We previously demonstrated that the combination of Remdesivir and Ivermectin is highly potent and synergistic in inhibiting the replication of murine hepatitis virus (MHV) in RAW264.7 macrophages. This study investigated the interactions between the drug combination, coronavirus and host by proteomics and RNA sequencing of MHV-infected H2.35 murine liver epithelial cells. Time-of-addition and time-of-removal assays suggested that the drug combination likely affected the synthesis of viral RNA and viral protein. This combination drastically diminished the live virus titer greater than the respective monotherapies in MHV-infected H2.35 cells (by ~4 log10), as well as in SARS-CoV-2-infected VeroE6 cells and human nasal epithelial cells. Proteomic and transcriptomic analyses revealed that viral protein and RNA levels were significantly depressed upon combination treatment. The drug combination exhibited considerable negative effects upon host RNA processes and resulted in the upregulation of host protein processes (e.g., response to unfolded protein; protein insertion into ER membrane). Molecular pathways affected by the combination treatment were markedly distinct from the monotherapies and indicated that Ivermectin enhances Remdesivir by modulating critical host processes to synergistically exert its inhibitory effect on the coronavirus replication cycle.</jats:p>",
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