Immunomodulatory and anti-cytokine therapeutic potential of curcumin and its derivatives for treating COVID-19 – a computational modeling

Abstract

The unavailability of vaccine and medicines raised serious issues during COVID-19 pandemic and peoples from different parts of world relied on traditional medicine for their immediate recovery from COVID-19 and it found effective also. The current research aims to target COVID-19 immunological human host receptors i.e. angiotensin-converting enzyme (ACE)-2, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) and protease-activated receptor (PAR)-1 using curcumin derivatives to prevent viral infection and control overproduction of early clinical responses of COVID-19. Targeting these host proteins will mitigate the infection and will filter out many complications caused by these proteins in COVID-19 patients. It is proven through computer-aided computational modeling approaches, total 30 compounds of curcumin and its derivatives were chosen. Drug-likeness parameters were calculated for curcumin and its derivatives and 20 curcumin analogs were selected for docking analysis. From docking analysis of 20 curcumin analogs against five chosen human host receptor targets reveals 11 curcumin analogs possess least binding affinity and best interaction at active sites subjected to absorption, distribution, metabolism, excretion (ADME) analysis. Density functional theory (DFT) analysis of five final shortlisted curcumin derivatives was done to show least binding affinity toward chosen host target protein. Molecular dynamics simulation (MDS) was performed to observe behavior and interaction of potential drug hydrazinocurcumin against target proteins ACE-2 and PAR-1. It was performed at 100 nanoseconds and showed satisfactory results. Finally, our investigation reveals that hydrazinocurcumin possesses immunomodulatory and anti-cytokine therapeutic potential against COVID-19 and it can act as COVID-19 warrior drug molecule and promising choice of drug for COVID-19 treatment, however, it needs further in vivo clinical evaluation to commercialize as COVID-19 drug.

Communicated by Ramaswamy H. Sarma

Keywords:

• ACE-2
• COVID-19
• curcumin
• cytokines
• IL-1β
• IL-6
• TNF-α
• PAR-1
• SARS-CoV-2

Acknowledgments

The authors would like to thank the Department of Biotechnology, Sona College of Arts and Science, Salem (District), Tamil Nadu, India and Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Punjab, Pakistan for their technical support.

Disclosure statement

The authors declare that they do not have any conflict of interest.

Figure 1. Docking pose and interaction plot for TNFα–di-O-acetyldemethoxy curcumin.

Figure 2. Docking pose and interaction plot for ACE-2–hydrazinocurcumin.

Figure 3. Docking pose and interaction plot for PAR-1–hydrazinocurcumin.

Figure 4. Binding pocket and active sites of PAR-1, ACE-2 and TNF-α COVID-19 host target proteins.

Figure 5. DFT study of di-O-acetyldemethoxy curcumin.

Figure 6. DFT study of hydrazinocurcumin.

Figure 7. Graph shows the ACE-2 (left y-axis) and hydrazinocurcumin (right y-axis) RMSD measure during the whole course of simulation.