2.2.3. Flaviviruses
Hepatitis virus, an RNA virus belonging to the Flaviviridae family, is closely related to liver disease, which in 70–80% of patients becomes chronic, resulting in major complications such as cirrhosis and, in the year, also liver cancer. The antiviral activity of HCQ on the hepatitis C virus (HCV) in monotherapy has not been tested. However, it seems that this drug increases the antiviral effect of standard drugs. In a study including 120 Egyptian patients infected by the hepatitis C virus, it was seen that the combination of HCQ with pegylated interferon and ribavirin could improve biochemical and virological responses in chronic hepatitis C subjects. All patients were randomized and divided into two groups; the control group treated with standard-of-care (SOC) consisted of 160 µg of subcutaneous pegylated interferon and 1000–12000 mg/day of oral ribavirin, and the group treated with 200 mg HCQ plus SOC. At the end of the treatment (12 weeks), patients of HCQ + SOC group showed a high virological response compared to the control group (54/60 (90%) vs. 43/60 (71.7%); p = 0.011). Moreover, in the HCQ + SOC group, there was a normalization of ALT levels, as is also demonstrated by the earlier biochemical response (EBR) highlighted in HCQ + SOC group 58/60 (96.7%) than SOC group 42/60 (70%) [30]. These results were confirmed by several case reports regarding patient treatment with Porphyria Cutanea Tarda and Hepatitis C. It was seen that a low dose of HCQ (100 mg twice weekly) prevented the recurrence of Porphyria Tarda and reduced the viral response during HCV therapy, including ribavirin and interferon [45]. Furthermore, in a patient with chronic hepatitis and rheumatoid arthritis, a low risk for hepatitis virus reactivation was observed after treatment with steroids (< 7.5 mg/day), HCQ or sulfadiazine [46] in combination with antivirals as prophylaxis [47,48].
Another possible antiviral effect of HCQ is exerted on Zika virus (ZIKV), an RNA virus of the Flaviviridae family transmitted by numerous mosquitoes of the genus Aedes. No clinical studies have been conducted yet, but an in vivo study has demonstrated the ability of HCQ to attenuate vertical transmission of ZIKV by reducing placental and fetal infection. In this study, pregnant mice were treated with 40 mg/kg/day HCQ via intraperitoneal injection beginning one day after ZIKV infection. It was seen that HCQ acted as an autophagy inhibitor by increasing p62 levels in trophoblast and thus reducing placental ZIKV infection and fetal growth defects [31]. To date, no clinical trials have been conducted to evaluate HCQ antiviral effects in patients infected by ZIKV.