Globally, coronavirus disease 2019 (COVID-19) outbreak caused a huge infection in all type of populations and fatalities as well as the worst disruptions to economies and societies since the great depression. In response to this terrible epidemic, it’s a great opportunity for experimental and computational research to be undertaken in an effort to characterize and know the disease scientifically in order to expeditiously discover diagnostic tools, vaccines, treatments, etc. Due to an unprecedented global health crisis, the urgent need for effective treatments became paramount. Drug discovery represents the scientific endeavor to identify, develop, and validate therapeutic actions that can alleviate the severity of illness, reduce mortality, and ultimately curb the outbreak of viral pathogens. In the backdrop of coronavirus-2 (SARS), this chapter explores the complex landscape of drug discovery while illustrating the numerous tactics used to battle the pandemic. The chapter explores an overview of the virus’s structure and pathophysiology and the challenges posed by the variability of symptoms and severity of disease. Examining the necessity of identifying and confirming molecular targets for drug development, computational biology’s contribution to this effort is emphasized. The chapter goes on to elucidate the methodologies of drug screening, both traditional and innovative, including the repurposing of existing drugs, which shows key principles to develop in the early pandemic stage only. A significant section describes how structure-based drug design is integrated and how knowledge of the structure of viral proteins in 3-D has impacted the logical development of potential therapies. COVID-19 drug discovery has yielded both positive and negative outcomes. While some medications, like remdesivir, dexamethasone, and monoclonal antibodies, have demonstrated promise in particular situations, others, such as hydroxychloroquine, did not show the anticipated advantages. The pandemic’s continual evolution highlights the significance of ongoing investigation and modification in the pursuit of efficient therapeutics. In essence, this chapter offers a thorough look into the complex realm of COVID-19 drug research, illuminating the exceptional cross-disciplinary cooperation that has shaped the scientific approach to an ongoing worldwide crisis with an emphasis on socioeconomic status.