Proteome-Based Investigation Identified Potential Drug Repurposable Small Molecules Against Monkeypox Disease

Area of Science:

• Virology
• Drug Discovery
• Computational Chemistry

Background:

• Monkeypox Virus (MPXV) is an emerging zoonotic pathogen causing outbreaks globally.
• Current MPX treatments like Cidofovir and Tecovirimat have side effects and risk resistance.
• Novel therapeutic strategies are essential to combat MPXV infections.

Purpose of the Study:

• To identify potential drug candidates for Monkeypox Virus (MPXV) through repurposing existing drugs.
• To screen the MPXV proteome for novel therapeutic targets and binding molecules.
• To evaluate the efficacy of identified compounds using computational methods.

Main Methods:

• DrugBank and ChEMBL databases were screened for potential MPXV drug candidates.
• Molecular docking and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses were performed.
• Molecular Dynamics (MD) simulations were utilized to assess compound-target interactions.

Main Results:

• Zidovudine and a Harmala alkaloid showed strong binding affinity to the L2R receptor (Thymidine Kinase).
• Fludarabine and 5 -Dehydroadenosine exhibited significant interaction with the I4L receptor (Ribonucleotide reductase large subunit R1).
• MD simulations indicated that these compounds can alter the structural dynamics of L2R and I4L proteins.

Conclusions:

• Zidovudine, a Harmala alkaloid, Fludarabine, and 5 -Dehydroadenosine are promising candidates for MPX drug repurposing.
• These identified small molecules warrant further in vitro and in vivo investigation for clinical applications.
• The study provides a computational basis for developing new treatments against Monkeypox Virus.