**1. Introduction**

The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (*SARS-CoV-2*), signifies a pandemic threat to international health, with so far nearly 5 million deaths worldwide [1]. Notwithstanding mass vaccination worldwide by emergency approved vaccines such as Pfizer-BioNTech, Janssen, and Moderna, COVID-19 still poses a threat to human health. Furthermore, with the emergence of new mutant strains of SARA-CoV-2 as well as a significant decrease in the vaccine's efficacies, introducing of new treatment strategies is urgently needed. Therefore, recently many international efforts have been planned for introducing suitable vaccines as well as effective therapeutics [2, 3].

Generally, time is a vital factor in the pandemic condition, so that, rapid detection, vaccination, and treatment methods can significantly reduce mortality. De novo drug discovery and development for lesser-known diseases such as COVID-19 is costly and tedious. Consequently, alternative methods such as the computational drug repurposing approach can accelerate the discovery of new drugs. In this regard, several pipelines have been introduced for in silico drug repositioning against COVID-19. Lately, molecular docking as a popular bioinformatics method has been highly regarded as the core of the most drug repositioning process to achieve effective drug candidates to combat COVID-19 [4–6]. In this chapter, we discussed new advancements and challenges in drug repositioning by molecular docking of pharmaceutical resources to the identification of potential *SARS-CoV-2* viral inhibitors.
