In vitro and in vivo studies reveal α-Mangostin, a xanthonoid from Garcinia mangostana, as a promising natural antiviral compound against chikungunya virus

Abstract

Background Chikungunya virus (CHIKV), a serious health problem in several tropical countries, is the causative agent of chikungunya fever. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. As diverse natural phenolic compounds have been shown to possess antiviral activities, we explored the antiviral activity of α-Mangostin, a xanthanoid, against CHIKV infection. Methods The in vitro prophylactic and therapeutic effects of α-Mangostin on CHIKV replication in Vero E6 cells were investigated by administering it under pre, post and cotreatment conditions. The antiviral activity was determined by foci forming unit assay, quantitative RT-PCR and cell-based immune-fluorescence assay. The molecular mechanism of inhibitory action was further proposed using in silico molecular docking studies. Results In vitro studies revealed that 8 µM α-Mangostin completely inhibited CHIKV infectivity under the cotreatment condition. CHIKV replication was also inhibited in virus-infected mice. This is the first in vivo study which clearly showed that α-Mangostin is effective in vivo by significantly reducing virus replication in serum and muscles. Molecular docking indicated that α-Mangostin can efficiently interact with the E2–E1 heterodimeric glycoprotein and the ADP-ribose binding cavity of the nsP3 macrodomain. Conclusions The findings suggest that α-Mangostin can inhibit CHIKV infection and replication through possible interaction with multiple CHIKV target proteins and might act as a prophylactic/therapeutic agent against CHIKV.

In Vitro Antiviral Activity of α-Mangostin against Dengue Virus Serotype-2 (DENV-2)

“…In the present study, though the antiviral activity of α-Mangostin was assessed against only DENV-2, the compound needs to be tested against the other serotypes as well. Our earlier study had shown that α-Mangostin inhibits chikungunya virus (CHIKV) in infected C57BL/6 mice [ 43 ]. Since CHIKV and DENV infection results in similar types of clinical symptoms, α-Mangostin might be a promising candidate for treatment of dengue-like illness.…”

Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models

“…In general, most of the studies use C57BL/6J wild type (WT) mice and CHIKV inoculation might occur from newborns at just few days after birth up to elderly animals of up to 48 weeks old. Likewise, virus titer can range from 10 2 to 10 8 plaque-forming unit (pfu)/ml (Gardner et al, 2010;Bosco-Lauth et al, 2015;Uhrlaub et al, 2016;Abdelnabi et al, 2018;Arévalo et al, 2019;Jain et al, 2019;Adam et al, 2021;Patil et al, 2021). Therefore, it is clear that the existence of a diversity of CHIKV rodent models and not surprisingly divergent outcomes is observed in each of them.…”

“…In contrast, after subcutaneous injection of 2 × 10 7 pfu/ml in 8-week-old C57BL/6J mice in the hind limbs, it was found replicating virus particles only until Uhrlaub et al, 2016;Arévalo et al, 2019;Jain et al, 2019 Anti-CHIKV treatment WT C57BL/6, C1q −/− , FcRγ −/− Limitation on CHIKV infection. Abdelnabi et al, 2018;Fox et al, 2019;Patil et al, 2021 Arthritis WT C57BL/6, ISG15 −/− , UbE1L −/− , MHCII / , IFNγ −/− , Sting gt/gt , CCR2 −/− CHIKV arthritis signature. Gardner et al, 2010;Werneke et al, 2011;Nakaya et al, 2012;Poo et al, 2014a;Geng et al, Wang et al, 2011;Arévalo et al, 2019;Campos et al, 2019;López-Camacho et al, 2019;Chen et al, 2020;Adam et al, 2021 Chronic/Persistent model WT C57BL/6, CD8 α −/− , Batf3 −/− , Wdfy4 −/− , Rag1 −/− , µMT C57BL/6; Golden hamster Viral persistence in joint tissues.…”

Therapeutic potential of phytoconstituents of edible fruits in combating emerging viral infections

“…In vitro prophylactic effect of α‐mangostin (extracted from the pericarps of mangosteen) was significantly inhibited the replication of CHIKV in Vero E6 cells with the 100% reduction of virus titer at 8 μM concentration under cotreatment condition (Patil et al., 2021 ). Also, reduction of CHIKV replication in serum and muscles of infected mice models showed nearly 99% of reduction in CHIKV RNA copies with low and high dose of α‐mangostin.…”

“…Also, reduction of CHIKV replication in serum and muscles of infected mice models showed nearly 99% of reduction in CHIKV RNA copies with low and high dose of α‐mangostin. The molecular docking study revealed that α‐mangostin interacts with the E2‐E1 heterodimeric glycoprotein and the outcomes suggest that α‐mangostin can possibly inhibit the replication of CHIKV infection through multiple target proteins (Patil et al., 2021 ).…”