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All Journal Eksakta : Berkala Ilmiah Bidang MIPA Jurnal Sehat Indonesia (JUSINDO)
Ratnoglik, Suratno Lulut
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Agriculture, Biological Sciences & Forestry Astronomy Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Civil Engineering, Building, Construction & Architecture Computer Science & IT Dentistry Energy Engineering Environmental Science Health Professions Materials Science & Nanotechnology Mathematics Mechanical Engineering Medicine & Pharmacology Nursing Public Health Veterinary

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Identification of Antiviral Compounds against Hepatitis C Virus (HCV) targeting NS3 Protein by Pharmacophore Modeling, Molecular Docking, and ADMET Approach Rahayu, Ratih; Erlina, Linda; Ratnoglik, Suratno Lulut; Yasmon, Andi; Fadilah; Paramita, Rafika Indah
EKSAKTA: Berkala Ilmiah Bidang MIPA Vol. 24 No. 04 (2023): Eksakta : Berkala Ilmiah Bidang MIPA (E-ISSN : 2549-7464)
Publisher : Faculty of Mathematics and Natural Sciences (FMIPA), Universitas Negeri Padang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24036/eksakta/vol23-iss04/448

Abstract

Hepatitis C Virus (HCV) is a world health problem. HCV infection is initiated by various structural and non-structural proteins. The HCV NS3 protein has an important function in viral replication. The N-terminal domain of NS3 acts as a protease to process most of the viral polypeptides. NS3 also acts as an RNA helicase and NTPase and triggers liver fibrosis which accelerates the development of liver disease. Thus, this study aims to provide information on potential new antiviral candidates against HCV that target the NS3 protein. This study was conducted in-silico with a ligand-based and structure-based pharmacophore model to the cavity of the active protein site generated after virtual screening and molecular docking. The results of this study showed that three compounds, namely stigmasterol, gamma-mangostin, and erycristagallin, were found as HCV antiviral candidates that target the NS3 protein with a lower binding affinity than the native ligand. The binding energy of each compound is -9.23 Kcal/mol, -8.58 Kcal/mol, and -8.17 Kcal/mol. Based on ADMET analysis, the three compounds have high absorption in the small intestine. The cytotoxicity analysis of stigmasterol compounds is not potentially mutagenic, and the LD50 value of stigmasterol is also lower than other compounds.
Update on Hepatitis C Virus (HCV) Vaccine Candidates in Clinical Trials: A Systematic Literature Review Ratnoglik, Suratno Lulut; Harumdini, Matahari
Jurnal Sehat Indonesia (JUSINDO) Vol. 6 No. 02 (2024): Jurnal Sehat Indonesia (JUSINDO)
Publisher : CV. Publikasi Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59141/jsi.v6i02.179

Abstract

Introduction: Hepatitis C virus (HCV) infection remains a significant global health challenge, affecting over 71 million people worldwide and leading to severe liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Despite the availability of highly effective direct-acting antiviral (DAA) therapies achieving sustained virologic response (SVR) rates exceeding 90%, high costs and limited accessibility impede global eradication efforts. Additionally, DAAs do not confer immunity against reinfection, highlighting the need for a prophylactic vaccine. Methods: This systematic literature review follows the PRISMA guidelines. A comprehensive search was conducted in PubMed, Scopus, and Web of Science for articles published between January 2010 and March 2024, focusing on HCV vaccine candidates in clinical trials. Data on study characteristics, participant demographics, vaccine characteristics, vaccine platforms and key outcomes were extracted. Results: Nine studies met the eligibility criteria, covering various phases of clinical trials (Phase I, II, and II/III). Key findings included: Vaccine platforms: The studies primarily utilized three types of vaccine platforms: Viral Vector-Based Vaccines, Peptide-Based Vaccines and Recombinant Protein Vaccines Immunogenicity: Vaccines targeting non-structural proteins (NS3, NS4, NS5) induced robust T-cell responses. Chimpanzee adenovirus (ChAd) and Modified Vaccinia Ankara (MVA) vector-based vaccines showed high polyfunctional CD8+ and CD4+ T-cell levels. Safety: Most adverse events were mild to moderate, including flu-like symptoms and injection site reactions. Severe adverse events were noted with TG4040 when combined with PEG-IFNα and RBV. Efficacy: Significant reductions in viral load and improvements in liver function were reported. Personalized peptide vaccines demonstrated enhanced immune responses and improved overall survival in HCV-positive advanced HCC patients. Conclusion: HCV vaccine development has made significant strides, with several candidates demonstrating strong immunogenicity, acceptable safety, and promising efficacy in clinical trials. Continued research is essential to address challenges such as viral genetic variability, durability of immune responses, and global accessibility.
Co-Authors Andi Yasmon Erlina, Linda Fadilah Harumdini, Matahari Paramita, Rafika Indah Rahayu, Ratih