Identification of doxorubicin as a potential therapeutic against SARS-CoV-2 (COVID-19) protease: a molecular docking and dynamics simulation studies

Sajid Jamal, Qazi Mohammad; Alharbi, Ali H.; Ahmad, Varish

After one year, the COVID-19 pandemic caused by SARS-CoV-2 is still the largest concern for the scientific community. Of the many recognized drug targets of SARS-CoV-2, the main protease is one of the most important target due to its function in viral replication. We conducted an in silico study with repurposing drugs of antibiotics class against virus protease and peptidase using AutoDock tool. The following significant binding energy interaction was observed with protease (PDB: 6LU7) like piperacillin –7.25; tobramycin –9.20 and doxorubicin (Doxo) –10.04 kcal/mol and with peptidase (PDB: 2GTB) piperacillin –7.08; tobramycin –8.54 and Doxo –9.89 kcal/mol. Furthermore, the interaction and stability behavior of the Doxo–protease and Doxo–peptidase complexes were analyzed for a 100-nanosecond (ns) time. Calculated RMSD values observed using molecular dynamics simulation (MDS) were found to be 0.15–0.25 nm, RMSF calculation per residues showed a value near 0.2 nm and R(g) values remained approximately 2.25 nm. MM-PBSA analysis of total binding energy calculation of Doxo–protease and Doxo–peptidase complexes are found to be –148.692 and –105.367 kJ/mol, respectively. Moreover, amino acid residue ASP-197 showed the lowest contribution binding energy i.e. –18.1185 kJ/mol, and amino acid residue ASP-187 showed –17.0267 kJ/mol contribution energy. Thus, significant docking interaction and stable dynamicity of Doxo–protease complex with time was suggested that Doxo could be a choice to inhibit potentially the viral proteases that could prevent the entry inside the host cell to control the COVID-19 disease. Communicated by Ramaswamy H. Sarma