Drug repurposing and virtual screening of antimicrobial agents against Mpox viral proteins using docking and molecular dynamics, and ADME-toxicity analysis

The rising incidence of Mpox cases calls for urgent and concerted efforts to identify effective therapeutics in the treatment of the disease. This research article explores standard antimicrobial agents as potential inhibitors of Mpox through in silico analysis targeting the 8CEQ protein, which is key in the survival of the virus. A comprehensive molecular docking approach was employed to assess the binding affinities of 21 common antimicrobial agents used in the treatment of various bacterial infections. This was subsequently followed by ADMET profiling, oral bioavailability analysis, and bioactivity assessments. Twelve (12) ligands were screened for critical properties influencing drug-likeness, including molecular weight, polar surface area, lipophilicity, flexibility, and solubility. Ceftriaxone had the highest binding affinity at -8.1 kcal/mol, followed by Cefepime (-7.5 kcal/mol). The Molecular Dynamics Simulation (MDS) results of the Ceftriaxone_8ceq and Cefepime_8ceq complexes validate their stable interactions in the active site of the Mpox drug target, although Cefepime_8ceq complex was more stable than the Ceftriaxone_8ceq complex. Overall, our findings suggest that Cefepime, Ceftriaxone, Nitrofurantoin, Trimethoprim, Gentamycin, and Cefotetan demonstrate promising inhibitory potentials against Mpox. These results underscore the utility of in silico methodologies in rapid drug repurposing efforts for emerging viral infections. While noting that most of the antimicrobial agents involved in the study were used not only orally but also through other routes of administration, the spectrum of findings suggests that though they have potential for the inhibition of the viral infection, further optimization and development of the identified ligands is required towards the development of reliable and safer novel anti-Mpox therapeutic agents.