Antiviral potential of Tualang honey in Chikungunya virus-infected human synoviocytes

Chikungunya is a mosquito-borne viral disease caused by chikungunya virus (CHIKV), characterised by fever, polyarthralgia, myalgia, rash, and headache, with chronic arthralgia persisting for months or years. Although vaccine is recently available, it is not widely used, and treatment focuses on symptom relief. Many natural products or their active compounds have been investigated for their anti-CHIKV activities on Vero cells which is irrelevant in CHIKV pathogenesis in human. Tualang Honey has also been shown to exert anti-CHIKV in Vero cells. This study advances the evaluation of Tualang honey's antiviral activity against CHIKV by utilising human fibroblast-like synoviocyte (HFLS) cells, a model more reflective of joint pathology in chronic infection. The maximum non-toxic dose (MNTD) of honey was determined using XTT assay. The effects of different concentrations and incubation times of honey were explored using pre-treatment and post-treatment assays, while anti-adsorption and anti-entry assays were used to investigate its antiviral activities. The MNTD of Tualang honey on HFLS cells was determined to be 50 mg/mL. Tualang honey at concentrations < 20 mg/mL exhibited variable prophylactic activity in the pre-treatment assay, reducing viral titres by 29.21% to 94.87%. Significant CHIKV inhibition (p < 0.05) was observed with 10 and 15 mg/mL pre-treatment for 6 and 12 hours before infection, respectively. Notably, its anti-CHIKV effects were stronger during pre-treatment than post-treatment assay. Posttreatment with honey caused minimal to strong CHIKV inhibition, lowering viral titres by 6.67%-72.46%, depending on the concentration and incubation time, although it was not statistically significant. Tualang honey showed stronger anti-entry than anti-adsorption effects, decreasing viral titres by up to 90.45% and 66.89%, respectively. This study highlights Tualang honey's anti-CHIKV activity through various mechanisms, although further research is needed to confirm its clinical relevance. Importantly, the effects of concentration and incubation time are essential factors in determining antiviral efficacy.