Introduction: The world is currently facing a pandemic caused by the new coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. Viral transcription and replication are within the fundamental processes of any virus. They allow the synthesis of genetic material and the consequent multiplication of the virus to infect other cells or organisms. Methods: The most important protein in SARS-CoV-2 is the RNA polymerase (RdRp or nsp12), responsible for both processes. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for drug search, like virtual screening and molecular docking. Here, Pathogen Box database of chemical compounds was used together with Remdesivir, Beclabuvir, and Sofosbuvir drugs as potential inhibitors of nsp12. Results: The results showed a Top10 potential target inhibitor, with binding energy (∆G) higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with ∆G = −7.53 kcal/mol, present interactions with three important residues of the nsp12 catalytic site. Conclusion: These proposed ligands would be used for subsequent validation by molecular dynamics, where they can be considered as drugs for the development of effective treatments against this new pandemic.