The rabies virus phosphoprotein and polymerase are both important targets for antivirals and are currently used to create the vaccine used for domestic and wild animals.

[14] When the structure of the L-P protein was analyzed using UCSF Chimera, it was found that it contained two zinc molecules as well as 2 five-membered rings.

[16] One of the domains in the L protein is responsible for speeding up the reaction that results in the capping of the RNA and thus could possibly be another good target for an antiviral drug.

[21] After receptor binding, Rabies lyssavirus enters its host cells through the endosomal transport pathway.

Inside the endosome, the low pH value induces the membrane fusion process, thus enabling the viral genome to reach the cytosol.

Both processes, receptor binding and membrane fusion, are catalyzed by the glycoprotein G which plays a critical role in pathogenesis (mutant virus without G proteins cannot propagate).

Later in infection, the activity of the polymerase switches to replication in order to produce full-length positive-strand RNA copies.

[8] In September 1931, Joseph Lennox Pawan of Trinidad found Negri bodies in the brain of a bat with unusual habits.

[22][23][24] Rabies virus is primarily transmitted through the bite of a rabid animal, allowing it to penetrate the skin, infect tissues, and neurons through their nerve endings and spreading to the nervous system.

[25][26][27][28] The retrograde axonal transport of Rabies lyssavirus to the central nervous system (CNS) is the key step of pathogenesis during natural infection.

The salivary glands located in the tissues of the mouth and cheeks receive high concentrations of the virus, thus allowing it to be further transmitted due to projectile salivation.

[31] The first symptoms of rabies may be very similar to those of the flu, including general weakness or discomfort, fever, or headache.

There may be also discomfort or a prickling or itching sensation at the site of bite, progressing within days to symptoms of cerebral dysfunction, anxiety, confusion, and agitation.

This long incubation period is most likely due to the presence of microRNA, which slow down viral replication in the muscles.

The central nervous system is the most prevalent in some cases and includes symptoms like headache, vertigo, anxiety, nightmares, depression, and more.

The neurological dysfunction starts when the central nervous system begins to slow and not function properly.

To differentiate street rabies variants, monoclonal antibodies identified origins in host reservoirs throughout the world.

Specific regions of the G protein have been shown to be most antigenic in leading to the production of virus neutralizing antibodies.

Previous work has demonstrated that antigenic sites II and III are most commonly targeted by natural neutralizing antibodies.

[42] Genotype 1 evolved in Europe in the 17th century and spread to Asia, Africa, and the Americas as a result of European exploration and colonization.

[43] The rabies virus appears to have undergone an evolutionary shift in hosts from Chiroptera (bats) to a species of Carnivora (i.e. raccoon or skunk) as a result of an homologous recombination event that occurred hundreds of years ago.

[44] This recombination event altered the gene that encodes the virus glycoprotein that is necessary for receptor recognition and binding.

[45] Recent research is focused on stabilizing the trimeric pre-fusion form of the rabies virus glycoprotein (RABV-G), which is the most immunogenic conformation of the protein.

This approach aims to develop vaccines that are both more cost-effective and have better protective coverage, addressing the ongoing global need for rabies prevention.

Rabies virus has also been used to create a vaccine against Ebola, called FiloRab1, and it was found to be 100% effective for nonhuman primates.