**4. Future perspectives and conclusion**

Bats always remain the source of attraction and fascinate humans. Even in Hollywood movies the character of the Dracula has been inspired from bats living on blood and coming out for the prey in night time. However, they became important to the medical community upon the first recognition of transfer of rabies virus to the animals serving as their prey for blood in 1959 in Trinidad. Since, then different have been suggested as the career for many viral pathogens that are responsible for different endemics, epidemics, and pandemics, including Nipah virus infection, Hendra virus infection, Ebola virus infection, SARS, MERS, and the current COVID-19 or SARS-CoV-2 infection. However, the direct causal virus for COVID-19, called SARS-CoV-2 has not been directly isolated from them, but genetically related or more close viruses have been identified in them [9, 10]. Hence, understanding the factors responsible for no severe pathogenic outcomes in the bats as compared to other mammals, including humans becomes crucial by keeping in mind the damages (both, life and economical) associated with current COVID-19 pandemic. The bat immune system has evolved in such a way to guard itself through the damages associated with high speed flight for long migration. For example, low ROS production to protect from DNA damage and inflammation. However, to keep a check on invading pathogens, especially viruses it has evolved the potent IFNdependent antiviral immune response without inducing severe pro-inflammatory immune response as seen in other mammals, including humans during Ebola virus and severe COVID-19 infection. A recent study has shown that the Ebola virus in humans and fruit bats (*Epomops buettikoferi*) evolves differently by undergoing short term evolution as studied through circular sequencing [122]. For example, the Ebola virus (EBOV) passaged in fruit bat (*E. buettikoferi*) cells shows a sequence markers specific for host RNA editing enzyme activity, including evidence for adenosine deaminase acting on RNA (ADAR) editing of the EBOV glycoprotein (GP), show increased G to A transitions depending on the EBOV genome strand, and increased average genomic Shannon entropy compared to Ebola virus passaged in human 293 T cells. The bat EpoNi/22.1 cells express approximately 12-fold more ADAR1 mRNA than 293 T cells due to unique features of bat cells or bats. Hence, host-specific factors, including ADAR impact mutation/evolution of the virus. Of note, the mutation rate for Ebola virus is same for both bat and human cell lines. Hence, studying and identifying bat-specific factors have a potential to answer the unknowns associated with mild or no infection with the same pathogen that proves lethal to humans. For example, the evolution of the pathogen in the reservoir host is drift-driven, but in the incidental host it favors positive selection to adapt and reduces the tropism for primary host (bats) [123]. Hence, the pathogen becomes severe in the incidental host and transmits among human hosts as seen in Ebola virus infection and COVID-19. Also, the virus related to the Rubella called Ruhugu virus (RuhV shares identical genomic structure with the Rubella virus) has also been isolated from cyclops leaf-nosed bats (*Hipposideros cyclops*) sampled in Uganda [124]. This indicates that Rubella virus may have evolved from bat virus or in future Rubella-like infection may affect humans and other mammals as zoonotic disease from bats. Thus the future zoonotic (bats-specific) infections-associated endemics, epidemics, and pandemics, including vampire bat (*D. rotundus*) rabies caused by vampire bat rabies virus (VBRV, Lyssavirus of Rhabdoviridae family) will depend on the host-pathogen evolutionary signatures or relationships [125].
