Table 2.
Therapeutic small molecules against NiV and HeV by drug name (and mechanism)
| Reference | Study design | Funder | |
|---|---|---|---|
| Ribavirin (nucleoside analogue prodrug) | Warrier et al (2020)39 | Clinical: compassionate use for treatment in NiV outbreak in Kochi, India, 2019 (n=1) | NA |
| Chandni et al (2020)40 | Clinical: compassionate use for treatment in NiV outbreak in Kerala, India, 2018 (n=12: 6 treated, 6 untreated) | ||
| Banerjee et al (2019)41 | Clinical: compassionate use for postexposure prophylaxis of health-care workers during NiV outbreak in Kerala, India, 2018 (n=8) | ||
| Kumar et al (2019)42 | Clinical: compassionate use for treatment in NiV outbreak in Kerala, India, 2018 (n=5) | ||
| Playford et al (2010)43 | Clinical: compassionate use during HeV outbreak in Australia, 2008, for treatment (n=2) and postexposure prophylaxis (n=1) | ||
| Chong et al (2001)44 | Clinical: compassionate use for treatment in NiV outbreak in Malaysia, 1998–99 (n=194: 140 treated, 54 untreated) |
||
| Rockx et al (2010)45 | Animal: African green monkey challenge with HeV (n=12) 4 × 105 TCID50 intratracheal for efficacy |
||
| Ribavirin (nucleoside analogue prodrug), 6-azauridine (orotidine monophosphate decarboxylase inhibitor), and rintatolimod (toll-like receptor 3 agonist interferon inducer) | Georges-Courbot et al (2006)46 | Animal: hamster challenge with NiV-M for efficacy (n=18) 350 × LD50 intraperitoneal Animal: hamster challenge with NiV-M for efficacy (n=18) 35 × LD50 intraperitoneal |
NA |
| Ribavirin (nucleoside analogue prodrug) and chloroquine (lysosome alkalinisation) | Freiberg et al (2010)47 | Animal: hamster challenge with NiV-M (n=41) and HeV (n=20) for efficacy (n=85) 104 TCID50 intraperitoneal |
US NIH |
| Chloroquine (lysosome alkalinisation) | Pallister et al (2009)48 | Animal: ferret challenge with NiV-M for efficacy and pharmacokinetics (n=8) 5 × 103 TCID50 oronasal |
US NIH |
| Remdesivir (nucleoside analogue) | de Wit et al (2023)49 | Animal: African green monkey challenge with NiV-B for efficacy (n=18) 105 TCID50 intranasal plus 105 TCID50 intratracheal |
US NIH |
| Lo et al (2019)50 | Animal: African green monkey challenge with NiV-B for efficacy (n=8) 105 TCID50 intranasal plus 105 TCID50 intratracheal |
||
| Jordan et al (2017)51 | Animal: African green monkey challenge with NiV-B for efficacy Lethal dose (unspecified) |
||
| Favipiravir (nucleoside analogue prodrug) | Dawes et al (2018)52 | Animal: hamster challenge with NiV-M for efficacy (n=18) 104 PFU intraperitoneal |
US NIH |
| Griffithsin (fusion and cell entry inhibitor) | Lo et al (2020)53 | Animals: hamster challenge with NiV-B for efficacy (n=65) 107 TCID50 intranasal |
US NIH and US CDC |
| Periodate heparin (competitive inhibitor of transinfection) | Mathieu et al (2015)54 | Animal: hamster challenge with NiV-M for efficacy (n=15) 500 × LD50 intraperitoneal |
INSERM |
| Fusion inhibitory lipopeptides (fusion and cell entry inhibitors): VIKI-dPEG4-Chol, VIKI-dPEG4-Toco, VG-PEG24-chol, and VIKI-PEG4-chol | Mathieu et al (2018)55 | Animal: hamster challenge with NiV-M for efficacy (n=38) 106 PFU (100 × LD50) intranasal Animal: African green monkey challenge with NiV-M for efficacy (n=10) 2 × 107 PFU intratracheal Animal: African green monkey biodistribution (n=4) |
US NIH and INSERM |
| Mathieu et al (2017)56 | Animal: hamster challenge with NiV-M for efficacy (n=13) 100 × LD50 intraperitoneal Animal: Hamster biodistribution (n=6) |
||
| Porotto et al (2010)57 | Animal: hamster challenge with NiV (strain unspecified) for efficacy (n=35) 100 × LD50 intraperitoneal |
||
| Defective interfering particles (virus-like particles containing defective interfering genomes that inhibit replication): DI-07, DI-10, DI-14, and DI-35 | Welch et al (2022)58 | Animal: hamster challenge with NiV-M for efficacy (n=153) Experiment 1: 104 TCID50 intraperitoneal Experiment 2: 106 TCID50 intranasal |
US CDC |
| Ceftriaxone (bacterial cell wall synthesis inhibitor), clarithromycin (bacterial protein synthesis inhibitor), and aciclovir (nucleoside analogue) | Paton et al (1999)11 | Clinical: empirical syndromic treatment during outbreak in Singapore, 1999 (n=11) | NA |
CDC=Centers for Disease Control and Prevention. dPEG=discrete polyethylene glycol. HeV=Hendra virus. INSERM=Institut National de la Santé et de la Recherche Médicale. LD50=median lethal dose. NA=not available. NIH=National Institutes of Health. NiV-B=Nipah virus Bangladesh. NiV-M=Nipah virus Malaysia. PFU=plaque-forming units. TCID50=median tissue culture infectious dose.
Please see appendix pp 12–16 for the full table.