Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections
Abstract
:1. Background
2. Enterovirus Classification
3. Virological Characteristics
4. Replicative Cycle
5. Current Strategies in Enterovirus Antiviral Research
5.1. Experimental Models
5.2. Broad-Spectrum and Adaptable Treatments
6. Emerging Antiviral Candidates for RV-D68 and RVs
6.1. Capsid Binders
6.1.1. Pleconaril
6.1.2. Pirodavir and Vapendavir
6.1.3. Pocapavir
6.1.4. R856932
6.1.5. Quinoline Derivative Compound 19
6.2. Viral Replication Protein Inhibitors
6.2.1. Telaprevir—2A Protease Inhibitor
6.2.2. Guadinine Hydrochloride and Fluoxetine—2C Protein Inhibitors
6.2.3. Rupintrivir and V-7404—3C Protease Inhibitors
6.2.4. Azvudine—3D Polymerase Inhibitor
6.2.5. Ribavirin—Guanosine Nucleoside Analog
6.2.6. Molnupiravir and EIDD-1931
6.3. Host Factors Antiviral
6.3.1. SAMHDI
6.3.2. Enviroxime and Vemurafenib—Pi4kiiiβ Inhibitor
6.3.3. CRT0066101, CRT0066051 and XX-050—Protein Kinase D Inhibitor
6.3.4. Itraconazole—OSBP Inhibitor
6.3.5. DAS181—Inhibitors Targeting the Cell Surface Sialic Acid Receptors
6.4. Antibodies
6.4.1. Human Antibodies
6.4.2. Non-Human Antibodies
6.5. Vaccines
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug Class | Antiviral Compound | Virus Targeted | Protein Targeted | Stage of Development | References |
---|---|---|---|---|---|
Capsid Binders | |||||
Pleconaril | RV, EV-D68 | VP1 | Phase II clinical trial for RV, Preclinical for EV-D68 | [79,80,81] | |
Pirodavir | RV | VP1 | Phase II clinical trial | [82,83] | |
Pocapavir (V-073) | RV | VP1 | Preclinical for RV and EV-D68, available for use in emergency treatment of severe neonatal EV-B infections | [84,85,86] | |
Quinoline derivative: Compound 19 | EV-D68 | Hydrophobic pocket of VP1 | Preclinical | [87] | |
R856932 (Tetrazole based) | EV-D68 | VP1 | Preclinical | [88] | |
Vapendavir | RV | VP1 | Phase II clinical trial | [89,90] | |
Viral replication protein inhibitors | |||||
Azvudine (FNC *) | EV-D68 | 3D | Approved in China for indication other than EV or RV infection | [91] | |
EIDD-1931, active form of molnupiravir | EV-D68 | 3D | EUA ** by FDA, approved in some countries for other infection than EV and RV | [92,93] | |
Fluoxetine | EV-D68 | 2C | FDA approved for indication other than EV or RV infection | [94,95] | |
Guanidine | EV-D68 | 2C | Preclinical | [96] | |
Ribavirin | RV | 3D | FDA approved for indication other than EV or RV infection | [97,98,99] | |
Rupintrivir (AG7088) | RV, EV-D68 | 3C | Phase II for RV | [100,101] | |
Telaprevir | EV-D68 | 2A | FDA approved for indication other than EV or RV infection | [102,103] | |
V-7404 | EV-D68 | 3C | Phase I | [104] | |
Host factors inhibitors | |||||
CRT0066101, CRT0066051 and XX-050 | RV | Protein Kinase D (PKD) | Preclinical | [105] | |
CUR-N399 | RV | PI4KIIIβ | Phase I | [106] | |
DAS181 | RV, EV-D68 | Sialic acid | Fast Track and Breakthrough Therapy designations by the FDA for indications other than EV or RV infection | [100,107,108] | |
Enviroxime | RV, EV-D68 | PI4KIIIβ | Phase II for RV, preclinical for EV-D68 | [109,110,111] | |
GSK3923868 | RV | PI4KIIIβ | Phase I | [112,113,114] | |
Itraconazole | RV | OSBP, ORP4 | FDA approved for indication other than EV or RV infection | [115,116] | |
KRP-A218 | RV | PI4KIIIβ | Phase I | [117] | |
SAMHD1 *** | EV-D68 | Cellular deoxynucleotide triphosphate (dNTP) | Preclinical | [118] | |
Vemurafenib | RV | PI4KIIIβ | FDA approved for indication other than EV or RV infection | [119] | |
Antibodies | |||||
A6-1 | EV-D68 | VP1 | Preclinical | [120] | |
EV68-159 | EV-D68 | VP1, VP3 | Preclinical | [121] | |
EV68-228 | EV-D68 | VP1 | Phase 1 | [121,122] | |
14C11 | RV | ICAM-1 | Preclinical | [66] |
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Rahajamanana, V.L.; Thériault, M.; Rabezanahary, H.; Sahnoun, Y.G.; Mallet, M.C.; Isabel, S.; Trottier, S.; Baz, M. Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections. Infect. Dis. Rep. 2025, 17, 61. https://doi.org/10.3390/idr17030061
Rahajamanana VL, Thériault M, Rabezanahary H, Sahnoun YG, Mallet MC, Isabel S, Trottier S, Baz M. Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections. Infectious Disease Reports. 2025; 17(3):61. https://doi.org/10.3390/idr17030061
Chicago/Turabian StyleRahajamanana, Vonintsoa L., Mathieu Thériault, Henintsoa Rabezanahary, Yesmine G. Sahnoun, Maria Christina Mallet, Sandra Isabel, Sylvie Trottier, and Mariana Baz. 2025. "Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections" Infectious Disease Reports 17, no. 3: 61. https://doi.org/10.3390/idr17030061
APA StyleRahajamanana, V. L., Thériault, M., Rabezanahary, H., Sahnoun, Y. G., Mallet, M. C., Isabel, S., Trottier, S., & Baz, M. (2025). Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections. Infectious Disease Reports, 17(3), 61. https://doi.org/10.3390/idr17030061