Abstract

Background:
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) represents a reproductive and respiratory disorder in pigs. Current application of various PRRSV vaccines demonstrated a partial activity against infection, and the role of curcumin in providing effective antiviral properties.

Aim:
Assessing the ability of curcumin and its analogs to inhibit PRRSV NSP4 using molecular docking.

Methods:
Curcumin structure was modified to increase bioavailability by removing the β-diketone unit and converting it to a monoketone. The structure of PRRSV NSP4 protein, which functions as a suppressor of NF-κB, was downloaded from the RCSB Protein Data Bank and prepared as a protein receptor. Then, all these analogs were screened using drug-likeness, Lipinski's Law of Five, ADMET, and molecular docking analyses to identify analogs with potential as PRRSV antivirals.

Results:
Curcumin compounds have been modified into 24 analogs: analogs A to X. Based on further analysis, analogs O and P were selected as the likely best antivirals for inhibiting PRRSV NSP4.

Conclusion:
Analog O and P have potential as drug candidates for PRRSV, as they indirectly inhibit NSP4. Therefore, these analogs are speculated to block NF-κB or adapter proteins in the host, including RIG-I, MDA5, and MAVS, thereby inducing IFN production. However, further testing is needed. Investigating molecular dynamics will reveal the bond stability between the analog compound and the protein, and in vivo testing will help determine the best route for applying this antiviral candidate.

Key words: Curcumin and its Analogs; IFN-β; Molecular Docking; NSP4 Protein; PRRSV.