The path towards effective antivirals against rabies

Area of Science:

• Virology
• Infectious Diseases
• Drug Discovery

Background:

• Rabies virus infection remains a major global health burden, causing an estimated 60,000 deaths annually, predominantly among children.
• While post-exposure prophylaxis (PEP) is effective, neurological rabies symptoms carry a fatality rate exceeding 99%.
• Previous attempts to develop effective rabies antivirals have shown limited success in human clinical trials.

Purpose of the Study:

• To explore novel therapeutic opportunities for identifying more potent anti-rabies virus molecules.
• To investigate the potential of antivirals developed for other Mononegavirales (e.g., paramyxoviruses, filoviruses) as rabies therapies.
• To identify antivirals suitable for both therapeutic (cerebrospinal fluid-dosed) and prophylactic (nerve cell infection prevention) use.

Main Methods:

• Review and exploration of existing antiviral research, particularly focusing on Mononegavirales.
• Analysis of requirements for effective therapeutic antivirals, including cerebrospinal fluid penetration and rapid replication blocking.
• Consideration of prophylactic antiviral strategies to prevent peripheral nerve cell infection and potentially replace current rabies immunoglobulins.

Main Results:

• Significant progress in developing antivirals against related viruses (paramyxoviruses, filoviruses) offers a promising avenue for rabies therapy.
• Identification of key characteristics for effective therapeutic antivirals: rapid, potent replication inhibition and cerebrospinal fluid accessibility.
• Potential for prophylactic antivirals to prevent initial nerve cell infection, offering an alternative to current immunoglobulin-based PEP.

Conclusions:

• Leveraging advancements in antivirals for related Mononegavirales presents a viable strategy to develop potent anti-rabies therapies.
• Development of novel therapeutic antivirals targeting cerebrospinal fluid is crucial for treating neurological rabies.
• Prophylactic antivirals could offer a new approach to rabies prevention, potentially improving upon existing post-exposure prophylaxis methods.