The COVID-19 pandemic caused by the SARS-CoV-2 virus has infected over 2 million people in Indonesia and has killed over 60 thousand. The urgency of the situation drove researchers to prevent the spread of SARS-CoV-2. One method to disinfect surfaces contaminated by SARS-CoV-2 is by attacking RdRp, an enzyme crucial to the virus’s life cycle. This in silico research has simulated molecular docking of copper oxide (CuO) and zinc oxide (ZnO) nanoparticles to determine the best nanoparticles for inhibiting the SARS-CoV-2 RdRp enzyme. The results of molecular docking were compared. The CuO nanoparticles obtained a docking score of -5.9 kcal/mol, whereas the ZnO nanoparticles obtained a docking score of -5.5 kcal/mole. Both nanoparticles show potential as antiviral agents against the SARS-CoV-2 RdRp enzyme. However, CuO nanoparticles have a better potential than ZnO nanoparticles. This study may serve as a reference to identify an antiviral agent suitable for disinfecting surfaces from SARS-CoV-2 contamination. © 2024 American Institute of Physics Inc.. All rights reserved.