Elucidating the Effects of Curcumin against Influenza Using In Silico and In Vitro Approaches

Abstract

The influenza virus is a constantly evolving pathogen that challenges medical and public health systems. Traditionally, curcumin has been used to treat airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate common targets of curcumin and influenza infection and underlying mechanisms, we employed network pharmacology and molecular docking approaches and confirmed results using in vitro experiments. Biological targets of curcumin and influenza were collected, and potential targets were identified by constructing compound–disease target (C-D) and protein–protein interaction (PPI) networks. The ligand–target interaction was determined using the molecular docking method, and in vitro antiviral experiments and target confirmation were conducted to evaluate curcumin’s effects on influenza. Our network and pathway analyses implicated the four targets of AKT1, RELA, MAPK1, and TP53 that could be involved in the inhibitory effects of curcumin on influenza. The binding energy calculations of each ligand–target interaction in the molecular docking showed that curcumin bound to AKT1 with the highest affinity among the four targets. In vitro experiments, in which influenza virus-infected MDCK cells were pre-, co-, or post-treated with curcumin, confirmed curcumin’s prophylactic and therapeutic effects. Influenza virus induction increased the level of mRNA expression of AKT in MDCK cells, and the level was attenuated by curcumin treatment. Collectively, our findings identified potential targets of curcumin against influenza and suggest curcumin as a potential therapy for influenza infection.

A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity

“…A recent study reported that curcumin inhibited SARS-CoV-2 D614G strain by pre-infection treatment of Vero E6 cells [ 12 ]. This effect has also been observed with other enveloped viruses including IVA [ 13 , 14 ]. Previous studies have reported that curcumin prevents SARS-CoV-2 entry by direct interaction with cell factors or viral proteins [ 15 , 16 ].…”

“…Plants are the major source for new drug discoveries to combat infectious disease [ 11 ]. Among these, curcumin is a promising candidate as it shows antiviral activity against both SARS-CoV-2 and IVA [ 12 , 13 ]. A recent study reported that curcumin inhibited SARS-CoV-2 D614G strain by pre-infection treatment of Vero E6 cells [ 12 ].…”

Curcumin as a natural potential drug candidate against important zoonotic viruses and prions: A narrative review

“…The whole IAV genome codes for different proteins including NA (neuraminidase), RNA polymerases (PB1, PB2, and PA), HA, M1 (matrix proteins), M2 (ion channel), and NP (nucleoprotein) (Hutchinson, 2018). In silico studies targeting NA, PB2, HA, M1, and M2, as well as different signaling pathways (AKT1, TP53, MAPK1, and RELA) illustrated that curcumin and its different derivatives act as acceptable inhibitors of these proteins and pathways (Jayasree et al, 2014; Kim, Choi, Kim, Kang, & Kim, 2021b; Richart et al, 2018; Roy et al, 2021; Satpathy et al, 2012; Singh & Misra, 2012).…”

Identification of the Tagetes erecta Linn. Extract’s potentials against influenza A based on bioinformatics analysis and experimental study

“…In uenza virus is an evolving pathogen that is a serious threat to medical and public health systems (14).…”