Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS

Hueffer, Karsten; Khatri, Shailesh; Rideout, S. A.; Harris, Michael B.; Papke, Roger L.; Stokes, Clare; Schulte, Marvin K.

doi:10.1038/s41598-017-12726-4

Cited by 45 publications

(62 citation statements)

References 33 publications

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“…This olfactory infection route scheme [18] has been recently extended to Covid-19 infection [2,11]. To further investigate the molecular aspects of Covid-19 propagation in the brain and its pharmacology, we have been aided by abundant studies on rabies virus (RABV) a negative polarity, single-strand RNA virus that is distinct from the coronaviruses [18][19][20]. nAChRs were shown to be the first receptors for RABV [21].…”

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confidence: 99%

“…nAChRs were shown to be the first receptors for RABV [21]. Structural studies further revealed that a short region in the ectodomain of the rabies virus glycoprotein shows sequence similarity to some snake toxins [20,22] that were initially used to isolate the nAChR from fish electric organs [23]. These snake toxins [24] are known to bind with high affinity and exquisite selectivity to the peripheral muscle receptor, while also to some brain receptors [25,26].…”

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confidence: 99%

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A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Changeux¹,

Amoura²,

Rey³

et al. 2020

Comptes Rendus. Biologies

222

127

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Background: Ivermectin is a widely used antiparasitic drug with known e cacy against several single-strain RNA viruses. Recent data shows signi cant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. Methods: An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology pro le including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic pro le of ivermectin in plasma and lungs was determined in all animals. Results: There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 grams/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean C max 86.2 ng/ml vs 26.2 ng/ml in the lower dose group and 152 ng/ml vs 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for lowdose females. Conclusion: nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.

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confidence: 99%

mentioning

confidence: 99%

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Changeux¹,

Amoura²,

Rey³

et al. 2020

Comptes Rendus. Biologies

222

127

View full text Add to dashboard Cite

show abstract

“…T his olfactory infection route scheme [18] has been recently extended to Covid-19 infection [2,11]. T o further investigate the molecular aspects of Covid-19 propagation in the brain and its pharmacology, we have been aided by abundant studies on rabies virus (RABV) a negative polarity, single-strand RNA virus that is distinct from the coronaviruses [18][19][20]. nAChRs were shown to be the first receptors for RABV [21].…”

mentioning

confidence: 99%

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Changeux¹,

Amoura

Rey

et al. 2020

Preprint

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SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. T here is a pressing urgency to find treatments based upon currently available scientific knowledge. T herefore, we tentatively propose a hypothesis which hopefully might ultimately help saving lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.

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“…In addition, answers from this survey indicated that hunting dogs would often chase wild dogs when an encounter did occur. Assuming an infection of rabies in the Australian wild dog population, which is known to induce severe aggressive behavioural changes in the host, such an encounter between a hunting dog and an infected wild dog might result in disease transmission through biting. In contrast to the results of this study, a previous survey of Australian hunters reported a high proportion (17%) of interviewed hunters who had witnessed attacks from wild dogs with their hunting dogs .…”

Section: Discussionmentioning

confidence: 99%

Hunting practices in northern Australia and their implication for disease transmission between community dogs and wild dogs

et al. 2019

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Objective This survey aimed to understand hunting practices involving domestic dogs in remote Indigenous communities in northern Australia and, in the context of disease transmission, describe the domestic–wild dog interface and intercommunity interactions of hunting dogs during hunting activities. Methods A cross‐sectional survey of 13 hunters from communities of the Northern Peninsula Area (NPA) of Queensland gathered information on demographics of hunters and hunting dogs, hunting practices and past encounters with wild dogs during hunting trips. Social networks that described the connections of hunters between NPA communities from hunting expeditions were developed. Results Most hunters interviewed were not aware of any diseases that could be transmitted to dogs (n = 11) or humans (n = 9) from wild animals while hunting. More than half (n = 7) of the respondents had experienced at least one wild dog encounter during hunting in the year prior to the interview. A map of the relative risk of interactions between wild and hunting dogs during hunting trips allowed the identification of high‐risk areas in the NPA; these areas are characterised by dense rainforests. The social networks at the community level resulted in relatively large density measures reflecting a high level of intercommunity connectedness. Conclusions This study contributes to our knowledge of Australian Indigenous hunting practices and supports the potential for disease transmission at the domestic–wild dog interface and intercommunity level through contacts between hunting dogs during hunting activities. Insights from this study also highlight the need for educational programs on disease management in Indigenous communities of northern Australia.

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Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS

Cited by 45 publications

References 33 publications

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Hunting practices in northern Australia and their implication for disease transmission between community dogs and wild dogs

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