Coronavirus, an infectious disease known as COVID-19, has become a pandemic affecting the respiratory system of humans and leads to fatal outcomes. It has been originated from Wuhan, China, and has spread all over the world. This virus shares similar clinical symptoms with the earlier viral infections, such as Severe acute respiratory syndrome (SARS-Cove) and the Middle East respiratory syndrome (MERS-CoV) infection; therefore, COVID-19 is also known as SARS-CoV-2. As of SARS-CoV, SARS-CoV-2 also utilizes the ACE-2 receptor to enter the host cell. These receptors are reported to present in the brain and cerebrospinal fluid. Moreover, various COVID-19 patients reported symptoms related to neuro, such as nausea, headache, tremor, etc. This finding shows that the virus is not only restricted to the respiratory system, but it also invades the CNS, which raises the interest to find its mechanism to enter the human brain cell and alteration of various brain Signalling pathways such as interferon, MAPK, JAK-STAT, and ACE-2/ANG-(1-7)/MAS caused by the novel coronavirus. Here, in this chapter, the recent updates regarding COVID-19 brain alterations and the possible brain targets to treat the SARS-CoV-2 disease have been discussed.