The Coronavirus Diseases 2019 (COVID-19) seriously affecting human health all over the world. More than 107 M people are reported positive for SARS-CoV-2, the virus causing COVID-19 pneumonia, from which +2.3 M died. Nucleotide Inhibitors (NI) have promising results in terms of its efficacy against different viral polymerases, including the Hepatitis C Virus (HCV) Non-Structural Protein 5 B (NS5B) RNA dependent RNA polymerase (RdRp) 1. Thus, the non-structural protein 12 (nsp12) RdRp of the human coronavirus represents an attractive target to develop a possible therapeutic agent. Sofosbuvir proved itself as a potential anti-SARS-CoV-2 RdRp and could inhibit viral replication and infection propagation.