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

Abstract

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

Multi-Level Biological Network Analysis and Drug Repurposing Based on Leukocyte Transcriptomics in Severe COVID-19: In Silico Systems Biology to Precision Medicine

“…Doxorubicin is a chemotherapeutic agent treating various types of cancer [ 143 ]. A study of structural bioinformatics revealed that doxorubicin proved the significant binding energy with SARS-CoV-2 main protease in the molecular docking [ 144 ]. This result suggested that doxorubicin could be a potential drug to treat severe COVID-19.…”

In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia ficus-indica with SARS-CoV-2 Mpro

“…two main amino acid residues also involved in the interaction of N3 inhibitor with the same protease target [56,65]. Interestingly, these two residues were also previously associated with the interaction of other molecules investigated as anti-COVID-19 drugs and endowed with M pro inhibitory activity [66,67].…”

“…We examined the astragalin-protease complex structure for the pose with the lowest binding energy by the ProteinPlus software and noticed that the plant compound was involved in multiple H-bonding, with residues Phe140 and Glu166 of the viral protein, two main amino acid residues also involved in the interaction of N3 inhibitor with the same protease target [56,65]. Interestingly, these two residues were also previously associated with the interaction of other molecules investigated as anti-COVID-19 drugs and endowed with M pro inhibitory activity [66,67].…”

Comprehensive investigation of RNA‐sequencing dataset reveals the hub genes and molecular mechanisms of coronavirus disease 2019 acute respiratory distress syndrome

“…Qazi et al. used Autodock to conduct computer simulations of the antibiotic class of viral proteases and peptidases and found that doxorubicin can be used to inhibit viral proteases that may prevent entry into host cells to control the COVID‐19 disease [ 45 ]. Bragi Lovetrue built an accurate COVID‐19 disease model.…”