Skip to content
DraconiticResearch
Search Sources API
189,105 studies31 sourcesUpdated 2 min ago
Peer-reviewedCC BYPLOS One

Erlotinib in a once-daily high-dose oral regimen could mitigate Chikungunya virus titer in mice

  • Chidinma Nelson Orji1,2
  • Naphat Loeanurit1,2
  • Akeanan Sroithongmoon3
  • Noppadol Wacharachaisurapol4
  • Yaowatree Jumroen5
  • Wanna Eiamart5
  • Supeecha Wittayalertpanya4,5
  • Weerachai Chaijamorn6,7
  • Tatta Sriboonruang6,7
  • Jirapat Vamananda6,7
  • Tanatorn Khotavivattana3
  • Siwaporn Boonyasuppayakorn1
7 affiliations
  1. 1Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
  2. 2Medical Science Program, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  3. 3Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
  4. 4Center of Excellence in Clinical Pharmacokinetics and Pharmacogenomics, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  5. 5Chula Pharmacokinetic Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  6. 6Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
  7. 7Pharmacometrics for Health Sciences Research Group, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Read full textPDFDOICite

Abstract

Chikungunya virus (CHIKV) is a re-emerging arbovirus that causes debilitating inflammatory arthritis, for which no approved antiviral therapy currently exists. This study investigated the potential of repurposing erlotinib, a tyrosine kinase inhibitor, as an anti-CHIKV agent. Erlotinib demonstrated promising in vitro antiviral activity, with EC50 values in the low micromolar range and a favorable selectivity index. However, in vivo evaluation in C57BL/6 mice revealed pharmacokinetic limitations, characterized by rapid absorption and clearance, resulting in insufficient drug exposure under standard dosing regimens. Escalation to an intensive four-times-daily (QID) regimen successfully maintained plasma concentrations above the in vitro therapeutic threshold but led to significant body weight loss and failed to reduce viral titers or viral RNA levels in infected tissues. However, a once-daily (OD) regimen improved tolerability and significantly reduced footpad and serum viral titers relative to vehicle-treated controls. Notably, despite the lack of virological control in the QID regimen, erlotinib treatment reduced leukocyte infiltration and tissue inflammation in both treatment regimens, indicating a host-directed immunomodulatory effect. Overall, these findings highlight the critical role of dosing frequency in determining erlotinib's in vivo antiviral efficacy against CHIKV and suggest that once-daily (OD) administration may represent a more viable dosing strategy for further evaluation of erlotinib as a host-directed antiviral against CHIKV. Future strategies should also explore combination approaches with direct-acting antivirals to achieve more viral suppression and mitigation of disease pathology, as well as Structure-Activity Relationship (SAR)-guided scaffold optimization to improve in vivo pharmacokinetic profiles.

Related

  1. Beyond the prohibition list: redirecting negative subsidies into positive incentives could mitigate overfishing and protect coastal communities in WTO fisheries reform
    Hollie Booth, Luky Adrianto
    EcoEvoRxivPreprintCC BY 4.0Full textEcologyEcoEvoRxiv
  2. In the synthetic biology era, engineered fungi could mitigate carbon dioxide emissions and enhance environmental resilience
    Kyle Davis, Joanna Tannous
    Communications Earth & EnvironmentPeer-reviewedCC BY 4.0Full textPlant biologyCrossrefDOAJ
  3. Could ergothioneine serve as an indicator of functional plant-AMF interactions in crop plants?
    Valter Weijola, Lena F. Nielsen, Benjamin Fuchs
    Frontiers in plant sciencePeer-reviewedCC BYFull textPlant biologyEurope PMC
  4. The potential of seafood to mitigate environmental impacts through diet choices
    Cheila Almeida, Yorgos Stratoudakis
    Environmental Research LettersPeer-reviewedCC BY 4.0Full textEcologyCrossref
  5. Chikungunya resurgence highlights gaps in Aedes surveillance and control in South America
    Vincent Corbel, Martha Ahumada, Tashanna Bowman +17
    The Lancet Regional Health - AmericasPeer-reviewedCC BY-NC-ND 4.0Full textGeneral biologyEpidemiology & public healthHAL

Cite

BibTeXRIS
BibTeX
@article{orji2026erlotinib,
  title = {{Erlotinib in a once-daily high-dose oral regimen could mitigate Chikungunya virus titer in mice}},
  author = {Chidinma Nelson Orji and Naphat Loeanurit and Akeanan Sroithongmoon and Noppadol Wacharachaisurapol and Yaowatree Jumroen and Wanna Eiamart and Supeecha Wittayalertpanya and Weerachai Chaijamorn and Tatta Sriboonruang and Jirapat Vamananda and Tanatorn Khotavivattana and Siwaporn Boonyasuppayakorn},
  journal = {PLOS One},
  year = {2026},
  month = nov,
  doi = {10.1371/journal.pone.0360169},
  url = {https://doi.org/10.1371/journal.pone.0360169},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Erlotinib in a once-daily high-dose oral regimen could mitigate Chikungunya virus titer in mice
AU  - Chidinma Nelson Orji
AU  - Naphat Loeanurit
AU  - Akeanan Sroithongmoon
AU  - Noppadol Wacharachaisurapol
AU  - Yaowatree Jumroen
AU  - Wanna Eiamart
AU  - Supeecha Wittayalertpanya
AU  - Weerachai Chaijamorn
AU  - Tatta Sriboonruang
AU  - Jirapat Vamananda
AU  - Tanatorn Khotavivattana
AU  - Siwaporn Boonyasuppayakorn
PY  - 2026
DA  - 2026/11/02
JO  - PLOS One
DO  - 10.1371/journal.pone.0360169
UR  - https://doi.org/10.1371/journal.pone.0360169
AB  - Chikungunya virus (CHIKV) is a re-emerging arbovirus that causes debilitating inflammatory arthritis, for which no approved antiviral therapy currently exists. This study investigated the potential of repurposing erlotinib, a tyrosine kinase inhibitor, as an anti-CHIKV agent. Erlotinib demonstrated promising in vitro antiviral activity, with EC50 values in the low micromolar range and a favorable selectivity index. However, in vivo evaluation in C57BL/6 mice revealed pharmacokinetic limitations, characterized by rapid absorption and clearance, resulting in insufficient drug exposure under standard dosing regimens. Escalation to an intensive four-times-daily (QID) regimen successfully maintained plasma concentrations above the in vitro therapeutic threshold but led to significant body weight loss and failed to reduce viral titers or viral RNA levels in infected tissues. However, a once-daily (OD) regimen improved tolerability and significantly reduced footpad and serum viral titers relative to vehicle-treated controls. Notably, despite the lack of virological control in the QID regimen, erlotinib treatment reduced leukocyte infiltration and tissue inflammation in both treatment regimens, indicating a host-directed immunomodulatory effect. Overall, these findings highlight the critical role of dosing frequency in determining erlotinib's in vivo antiviral efficacy against CHIKV and suggest that once-daily (OD) administration may represent a more viable dosing strategy for further evaluation of erlotinib as a host-directed antiviral against CHIKV. Future strategies should also explore combination approaches with direct-acting antivirals to achieve more viral suppression and mitigation of disease pathology, as well as Structure-Activity Relationship (SAR)-guided scaffold optimization to improve in vivo pharmacokinetic profiles.
SN  - 1932-6203
ER  -