Beyond ST-246: Unveiling Potential Inhibitors Targeting VP37 Protein in Silico From Herb and Marine Databases.

Area of Science:

• * Medicinal Chemistry
• * Computational Biology
• * Virology

Background:

• * Monkeypox virus (MPXV) poses a significant public health threat.
• * Existing treatments like ST-246 target viral proteins, necessitating the search for novel inhibitors.
• * The VP37 protein is a key target for antiviral drug development against MPXV.

Purpose of the Study:

• * To discover novel structural inhibitors targeting the MPXV VP37 protein.
• * To identify pharmaceutical molecules effective against monkeypox virus using in silico methods.
• * To find potential drug candidates that surpass the efficacy of ST-246.

Main Methods:

• * Employed semi-flexible molecular docking and molecular dynamics simulations.
• * Utilized ADME screening for in silico compound evaluation.
• * Screened compounds from the CMNPD and TCM databases.

Main Results:

• * Identified six top hit compounds with significant binding values and interactions with the VP37 protein's binding site.
• * Molecular dynamics simulations confirmed the stability of these interactions.
• * Five compounds demonstrated superior inhibitory activity compared to the reference ST-246.

Conclusions:

• * The identified compounds represent promising lead candidates for developing new monkeypox virus therapeutics.
• * These findings provide a foundation for further in vitro and in vivo validation.
• * The study highlights the potential of structure-based drug design against MPXV.