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Rabies Virus: Treatment and Prevention

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 20531

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Special Issue Editor

Prof. Dr. Paulo Eduardo Brandão

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Guest Editor

School of Veterinary Medicine, Department of Preventive Veterinary Medicine and Animal Health, University of São Paulo, São Paulo 05508-270, Brazil
Interests: rabies treatment; rabies pathogenesis; Lyssavirus rabies molecular biology; Virus-host coevolution

Special Issue Information

Dear Colleagues,

Rabies is a 100% lethal zoonotic encephalitis caused by species in the Lyssavirus, chiefly Lyssavirus rabies or Rabies virus (RABV), which leads to 55,000 human deaths each year; for rabies patients, who experience extensive suffering, no rational treatment is currently available. Any treatment must include the clearance of lyssavirus infection targeting either the virus itself or host factors, the recovery of the damaged neural tissues, and physiotherapy. Despite bold attempts to treat human patients with a combination of antivirals, this has resulted in few survivors, and although reports have shown that antivirals can impair RABV replication both in vitro and in vivo, the field of rabies treatment lags behind the progress for viral diseases mainly due to its neglect. Regardless of the efforts to control rabies in reservoirs and the availability of highly effective pre- and post-exposure immunoprophylaxis, developing a treatment for patients not reached by these preventive measures remains a duty for those in this field.

This Special Issue is designed to publicise in silico, in vitro, and in vivo experiments on antivirals against lyssaviruses, as well as results of clinical trials and innovative approaches to the prevention of rabies.

Prof. Dr. Paulo Eduardo Brandão
Guest Editor

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Keywords

rabies
antiviral
treatment
prevention

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Published Papers (5 papers)

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Research

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20 pages, 5354 KiB

Open AccessArticle

An Evaluation of the Anti-Rabies Effect of Bufotenine in Murine Rabies Models to Determine Its Mechanism of Action

by Patrícia Mariano Cruz Pereira, Andréa de Cássia Rodrigues Silva, Karen Miyuki Asano, Adriana da Costa Neves, Juliana Mozer Sciani, Daniel Carvalho Pimenta and Hugo Vigerelli

Viruses 2025, 17(6), 808; https://doi.org/10.3390/v17060808 - 31 May 2025

Viewed by 389

Abstract

Molecules from animals or plant species have been investigated with the aim of treating diseases of epidemiological importance, such as rabies, which is a viral, acute, and infectious disease with approximately 100% lethality. Rabies has been one of the main causes of death in humans concerning infectious diseases. This work investigated the action and preliminary mechanisms of the alkaloid bufotenine in an in vivo model with the rabies virus. A wild-type virus was titrated and injected into mice for the determination of DL50 in the presence or absence of bufotenine. The results reveal that bufotenine has possible action in modulating the immune response of the studied host, suggesting interference in delaying symptom manifestation. Regarding the histological analysis of the CNS of the animals, bufotenine possibly prevented the presence of mononuclear cell inflammatory infiltrate in the meninx’s region compared to the positive control and possibly contributed to reducing neuronal degeneration. The use of the bufotenine extracted from the seed of white angico, a plant representative of Brazilian flora, contributed to antiviral activity with effects on the immunological aspects of the host infected by the rabies virus. Full article

(This article belongs to the Special Issue Rabies Virus: Treatment and Prevention)

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15 pages, 1015 KiB

Open AccessArticle

Bat Bites and Rabies PEP in the Croatian Reference Centre for Rabies 1995–2020

by Radovan Vodopija, Ivana Lojkić, Daniela Hamidović, Jelena Boneta and Dora Primorac

Viruses 2024, 16(6), 876; https://doi.org/10.3390/v16060876 - 30 May 2024

Viewed by 2633

Abstract

Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human fatalities associated with bat injuries/bites. The study included a retrospective analysis of bat injuries/bites, post-exposure prophylaxis (PEP) and geographic distribution of bat injuries in persons examined at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies. In the period 1995–2020, we examined a total of 21,910 patients due to animal injuries, of which 71 cases were bat-related (0.32%). Of the above number of patients, 4574 received rabies PEP (20.87%). However, for bat injuries, the proportion of patients receiving PEP was significantly higher: 66 out of 71 patients (92.95%). Of these, 33 received only the rabies vaccine, while the other 33 patients received the vaccine with human rabies immunoglobulin (HRIG). In five cases, PEP was not administered, as there was no indication for treatment. Thirty-five of the injured patients were biologists or biology students (49.29%). The bat species was confirmed in only one of the exposure cases. This was a serotine bat (Eptesicus serotinus), a known carrier of Lyssavirus hamburg. The results showed that the bat bites were rather sporadic compared to other human injuries caused by animal bites. All bat injuries should be treated as if they were caused by a rabid animal, and according to WHO recommendations. People who come into contact with bats should be strongly advised to be vaccinated against rabies. Entering bat habitats should be done with caution and in accordance with current recommendations, and nationwide surveillance should be carried out by competent institutions and in close collaboration between bat experts, epidemiologists and rabies experts. Full article

(This article belongs to the Special Issue Rabies Virus: Treatment and Prevention)

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12 pages, 2187 KiB

Open AccessEditor’s ChoiceArticle

A Robust Phenotypic High-Throughput Antiviral Assay for the Discovery of Rabies Virus Inhibitors

by Xinyu Wang, Winston Chiu, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Johan Neyts and Dirk Jochmans

Viruses 2023, 15(12), 2292; https://doi.org/10.3390/v15122292 - 23 Nov 2023

Cited by 2 | Viewed by 3114

Abstract

Rabies virus (RABV) causes severe neurological symptoms in mammals. The disease is almost inevitably lethal as soon as clinical symptoms appear. The use of rabies immunoglobulins (RIG) and vaccination in post-exposure prophylaxis (PEP) can provide efficient protection, but many people do not receive this treatment due to its high cost and/or limited availability. Highly potent small molecule antivirals are urgently needed to treat patients once symptoms develop. In this paper, we report on the development of a high-throughput phenotypic antiviral screening assay based on the infection of BHK-21 cells with a fluorescent reporter virus and high content imaging readout. The assay was used to screen a repurposing library of 3681 drugs (all had been studied in phase 1 clinical trials). From this series, salinomycin was found to selectively inhibit viral replication by blocking infection at the entry stage. This shows that a high-throughput assay enables the screening of large compound libraries for the purposes of identifying inhibitors of RABV replication. These can then be optimized through medicinal chemistry efforts and further developed into urgently needed drugs for the treatment of symptomatic rabies. Full article

(This article belongs to the Special Issue Rabies Virus: Treatment and Prevention)

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Review

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10 pages, 664 KiB

Open AccessReview

Human Rabies Treatment—From Palliation to Promise

by Marian Lacy, Nonthapan Phasuk and Stephen J. Scholand

Viruses 2024, 16(1), 160; https://doi.org/10.3390/v16010160 - 22 Jan 2024

Cited by 7 | Viewed by 11146 | Correction

Abstract

Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies. Full article

(This article belongs to the Special Issue Rabies Virus: Treatment and Prevention)

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