Hepatitis C virus (HCV) infection is a major worldwide problem, which involves approximately 170 million people. High morbidity of patients is caused by chronic infection, which leads to liver cirrhosis, hepatocellular carcinoma and other HCV-related diseases. The sustained virological response (SVR) has been markedly improved to be >90% by the current standard interferon (IFN)-free treatment regimens with a combination of direct-acting antiviral agents (DAAs) targeting the viral NS3 protease, NS5A multi-function protein and NS5B RNA-dependent RNA polymerase, compared with 50–70% of SVR rates achieved by the previous standard IFN-based treatment regimens with or without an NS3 protease inhibitor. However, the emergence of DAA-resistant HCV strains and the limited access to the DAAs due to their high cost could be major concerns. Also, the long-term prognosis of patients treated with DAAs, such as the possible development of hepatocellular carcinoma, still needs to be further evaluated. Natural resources are considered to be good candidates to develop anti-HCV agents. Here, we summarize anti-HCV compounds obtained from natural resources, including medicinal plant extracts, their isolated compounds and some of their derivatives that possess high antiviral potency against HCV.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Dorf2-8, Δorf2.4, and Δorf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the Δorf2-8 and Δorf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the Δorf2.4-puro replicon by inserting a puromycin-resistant gene into the Δorf2.4 replicon. We observed the more sustained replication of the Δorf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.

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Objective: Toona sureni (Indonesian mahogany) is a member of Meliaceae family and locally known as suren. Previous study reported that T. sureni leaves extract exhibited antiviral activity with 50% inhibitory concentration (IC 50 ) value of 13.9 ± 1.6 µg/ml against hepatitis C virus (HCV) J6/JFH1. Cytotoxicity analysis of T. sureni leaves extract did not reveal any cytotoxicity effect; therefore, further study was taken to investigate the active substances from the extract.Methods: Bioassay-guided isolation of anti-HCV was conducted using Huh-7.5 cells infected with HCV J6/JFH1 in the presence of extracts, fractions, or compounds from the plant.Results: Ethyl acetate fraction (Fr E) exhibited high anti-HCV activity with IC 50 value of 1.7 µg/ml. Further, separation of Fr E by open column chromatography resulted in nine sub-fractions (sub-Fr E1-E9). Sub-Fr E3 and E4 have IC 50 value of 29.90 µg/ml and 7.68 µg/ml, respectively. Polyphenols compounds have been isolated from sub-Fr E3 and E4. The structures have been determined to be ethyl gallate (1), methyl gallate (2), catechin (3), gallic acid (4), and quercetin 3-O-rhamnoside (5). Among the isolated compounds, gallic acid showed to possess strong anti-HCV activity with IC 50 value of 15.9 µg/ml. Conclusion:T. sureni and its isolated compound, gallic acid, may be good candidates to develop for alternative and/or complementary agents of anti-HCV infection.