Artesunate, an anti-malarial drug, has a potential to inhibit HCV replication

Abstract

Hepatitis C virus (HCV) infection is a major global health issue. Although the search for HCV treatments has resulted in great achievements, the current treatment methods have limitations, and new methods and drugs for hepatitis C treatment are still required. The aim of the present study was to investigate the effects of artesunate (ART) on HCV replication and compared these effects with those of ribavirin (RBV) and interferon-2b (IFN). The study was performed in HCV-infection cell models (JFH1-infected Huh7.5.1 and OR6 cell lines). Our results showed that the antimalarial drug ART inhibited HCV replicon replication in a dose- and time-dependent manner at a concentration that had no effect on the proliferation of exponentially growing host cells, and the inhibitory effect on HCV replication was stronger than RBV but weaker than IFN, as determined by qPCR, luciferase assays, and Western blot analysis. Furthermore, the combination of ART and IFN resulted in a greater inhibition of HCV replication. These findings demonstrated that ART had an inhibitive effect on HCV replication and may be a novel supplemental co-therapy with IFN and RBV for HCV and as an alternative strategy to combat resistance mechanisms that have emerged in the presence of DAA agents.

The Use of Antimalarial Drugs against Viral Infection

“…As mentioned above, ART and AS were more active against HBV and less toxic than other compounds from traditional Chinese medicine [17]. The reduction in HCV replicons caused by AS was dose and time-dependent in vitro and increased when AS was given in association with IFN [57].…”

“…Flaviviridae BVDV(surrogate HCV) Artemisinin in vitro [187,188] Dihydroartemisinin in vitro [63] HCV Artemisinin in vitro [20][21][22] Artesunate in vitro [57] Chloroquine in vitro [148][149][150] ZIKV Mefloquine in vitro [130,131] Chloroquine in vitro [140,141] Amodiaquine in vitro [140] Atovaquone in vitro [166] DENV Quinine sulfate in vitro [66] Mefloquine in vitro [131] Halofantrine in vitro [134] Doxycycline in vitro [168,178] Amodiaquine in vitro [162] CHIKV Doxycycline in vitro [169] Chloroquine in vitro [37,138,139] Atovaquone in vitro [166] Togaviridae SFV Halofantrine in vitro [134] Rhabdoviridae VSV Doxycycline in vitro [170] Orthomyxoviridae IAV Quinine sulfate in vitro [70] In vivo (mouse) [67] Mefloquine in vitro [70] Doxycycline in vivo (mouse) [171] Chloroquine in vitro [159]…”

Artemisia annua, a Traditional Plant Brought to Light

“…Regarding RNA viruses, it has been demonstrated in vitro that artemisinin and its derivatives are also effective against single-stranded RNA viruses from the Flaviviridae family including Hepatitis C Virus (HCV) [ 245 , 246 , 247 ] and bovine viral diarrhea virus (BVDV) [ 248 , 249 ]. Co-treatment with hemin or ferrosanol resulted in enhanced anti- Flaviviridae activity of artemisinin derivatives (224).…”

Peroxides with Anthelmintic, Antiprotozoal, Fungicidal and Antiviral Bioactivity: Properties, Synthesis and Reactions

“…It was determined that artesunate ( 4 ) causes changes in the reproductive system of Fasciola hepatica [ 144 ]. Antiviral activity of artesunate is displayed against the hepatitis В virus [ 157 ] and the hepatitis C virus [ 158 ], the herpes virus (HHV) type 4 and type 6 [ 159 , 160 ], human cytomegalovirus (HCMV) [ 161 , 162 , 163 ], including therapy-resistant mutants of human cytomegalovirus [ 164 ]. Artesunate ( 4 ) is prepared by reaction of dihydroartemisinin ( 2 ) with succinic anhydride in basic conditions ( Scheme 35 ) [ 152 ].…”