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Remdesivir's second chance: A glimmer of hope in the fight against nipah virus.

Remdesivir protects lab animals from lethal disease if administered immediately after the infection. However, such swift treatment rarely mirrors real outbreak scenarios.


A recent Nipah virus study in monkeys tested remdesivir starting 3 days after exposure, reflecting more real-world treatment delays. The findings provide hope that this readily available medicine may offer at least partial clinical benefit.


Nipah virus – A deadly pathogen


Nipah virus likely originated in fruit bats across Asia. However, periodic spillover events transmit the virus to humans, often via contaminated food [1]. Outbreaks have struck South Asian countries like Bangladesh and India nearly every year since 2001 [2].


Initial symptoms include:

  • Fever

  • Headache

  • Cough

  • Vomiting

  • Muscle pain

  • Behavioral changes

  • Disorientation


Need for effective medication


Nipah virus

In around half of the cases, the infection progresses to the inflammation of the brain (called encephalitis). This advanced form causes dangerous complications like seizures, coma, and even death.


There are currently no approved vaccines or medications for the Nipah virus [2]. Supportive hospital care is the only option. With death rates reaching an alarming 75%, effective drugs are desperately needed [3].


Remdesivir: A promising antiviral against nipah


Researchers have been assessing various compounds that show promise in the labs for treating this dangerous infection. One antiviral drug called remdesivir has demonstrated particular potential in animal studies.


Remdesivir inhibits viral replication by mimicking the molecular building blocks viruses incorporate into new genome copies. Research confirms that remdesivir improves survival when given immediately after Nipah virus infection [4].


Scientists tested remdesivir with more delayed administration which better reflects real-world scenarios [5]. The goal was to assess if later treatment still improves survival outcomes for this aggressive infection.


Assessing the efficacy of delayed remdesivir in nipah virus


To test the efficacy of delayed remdesivir, scientists infected monkeys with a lethal Nipah virus dose and then split them into three groups:

  • Group 1: Received 11 days of intravenous remdesivir starting on day 3 post-exposure. Initial higher loading dose, then lower daily maintenance doses.

  • Group 2: Given 12 days of the standard dose from day 3 onwards.

  • Group 3: Untreated controls for comparison.


Partial but promising efficacy when treatment was deferred


In the control arm, all 6 monkeys developed severe neurological disease and had to be euthanized around 21 days into infection. This confirmed the lethality of the Nipah challenge.


However, results showed that remdesivir treatment offered substantial protection even with the compromise of later delivery:

  • Four out of 6 monkeys (67%) survived in group 1

  • Only 2 out of 6 (33%) survived in group 2

Surviving animals still show minor brain inflammation. And without longer follow-up, potential later relapse remains unknown. However, significantly elevated survival despite starting therapy 72 hours after the exposure seems clinically meaningful.


The better outcomes with an initial higher than lower remdesivir dose suggest this regimen provides greater antiviral activity for Nipah infection.


Optimizing dosing will be critical


These findings imply that while earlier intervention is best, all hope is not lost for benefiting patients presenting later. However, every 12- or 24-hours dosing used for COVID-19 may not provide the sustained antiviral exposure needed for rapidly progressing Nipah infection.


Optimizing dose amount and duration will likely impact the results. Combining remdesivir with monoclonal antibodies or other drugs could also boost efficacy. One candidate antibody called m102.4 has shown marked survival advantages against the Nipah virus in animal studies [1].


Ongoing challenges & next steps


These latest findings provide a blueprint for optimizing dose and schedule to expand remdesivir's protective window in Nipah infection. Confirming efficacy when started 3 days after exposure supports its use even in remote settings where treatment delays are expected.


Developing remdesivir specifically for Nipah will require gathering more clinical data on disease progression rates and timelines in patients. This would allow better translation of animal experiment timing to expected human scenarios.


While research on better-targeted compounds proceeds, repurposing remdesivir could save many lives during outbreaks of this formidable pathogen.


References


1. V. Soman Pillai, G. Krishna, and M. Valiya Veettil, “Nipah Virus: Past Outbreaks and Future Containment,” Viruses, vol. 12, no. 4, p. 465, Apr. 2020, doi: 10.3390/v12040465.

2. A. R. Garbuglia, D. Lapa, S. Pauciullo, H. Raoul, and D. Pannetier, “Nipah Virus: An Overview of the Current Status of Diagnostics and Their Role in Preparedness in Endemic Countries,” Viruses, vol. 15, no. 10, p. 2062, Oct. 2023, doi: 10.3390/v15102062.

3. J. H. Epstein, H. E. Field, S. Luby, J. R. C. Pulliam, and P. Daszak, “Nipah virus: Impact, origins, and causes of emergence,” Curr Infect Dis Rep, vol. 8, no. 1, pp. 59–65, 2006, doi: 10.1007/s11908-006-0036-2.

4. M. K. Lo et al., “Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge,” Sci Transl Med, vol. 11, no. 494, p. eaau9242, May 2019, doi: 10.1126/scitranslmed.aau9242.

5. E. de Wit et al., “Late remdesivir treatment initiation partially protects African green monkeys from lethal Nipah virus infection,” Antiviral Res, vol. 216, p. 105658, Aug. 2023, doi: 10.1016/j.antiviral.2023.105658.

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