After the discovery of the infectious bronchitis virus (IBV) in 1932, Coronaviridae emerged as a family of viruses constituted of a positive-sense singlestranded RNA ((+)ssRNA) genome. Recently, the Coronavirus disease-2019 (COVID- 19), which is caused by a new virus called SARS-CoV-2 (provisionally titled 2019- nCoV), was declared pandemic since it reached global levels of infection. In comparison, this disease spread globally more quickly than previously reported SARS and MERS-CoV outbreaks. The impacts on global health systems (as well as the world economy, estimated to cost US$ 1 trillion) highlighted the urgent need to search for efficient pharmacotherapy targeting potential macromolecules from SARS-CoV-2 since there are no licensed vaccines or approved drugs until today. In this chapter, we will demonstrate all strategies that have been used to discover and design bioactive molecules against this viral infection, compiling from classical to computer-aided drug design, including also the drug repurposing. This last, it is based on analogs produced for past outbreaks related to SARS- and MERS-CoV. Finally, we aim to provide valuable information that could be applied for designing new safe, low cost, and selective lead-compounds against these emerging viruses.