Overview of hepatitis C infection, molecular biology, and new treatment

Rabaan, Ali A.; Al-Ahmed, Shamsah H.; Bazzi, Ali M.; Alsuliman, Shahab A.; Aldrazi, Fatimah A.; Haque, Shafiul

doi:10.1016/j.jiph.2019.11.015

Cited by 55 publications

(51 citation statements)

References 143 publications

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“…There are 7 major genotypes which are differed from each other by~25-35% at nucleotide level and 67 subtypes which differ from each other by~15-25% at the nucleotide level. The genotype 1 is the most frequent globally [3,4].…”

Section: Hepatitis C Virusmentioning

confidence: 99%

“…With NS3 helicase, it synthesizes a minus-strand RNA that serves as template for numerous plus-stranded RNA. The precise mechanism of viral assembly and release is not well understood, but it is believed that it is a multistep procedure involving several cellular factors and most of the viral components [4][5][6] (Fig. 1).…”

Section: Hepatitis C Virusmentioning

confidence: 99%

“…Estimated worldwide frequency is 1-3%, with 70 million chronically infected people in 2017; fewer than 20% of those living with HCV are aware of their infection. There is no vaccine to prevent the infection [4][5][6][7].…”

Section: Epidemiology and Clinical Signsmentioning

confidence: 99%

“…Increased accurate, simple, rapid testing and harm reduction through needle-exchange and opioid-substitution therapy are likely to reduce the burden of viral hepatitis infection in both general and high-risk population groups. Increasing knowledge about viral cycling could provide further information to develop an effective vaccine, which is a challenge that still remains to be solved [2,4,6].…”

Section: Elimination Of Viral Hepatitis By 2030mentioning

confidence: 99%

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The Nobel Prize in Physiology or Medicine—2020

Hagymási

2021

Struct Chem

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At the time of COVID-19 coronavirus pandemia, the Nobel Prize of Physiology or Medicine 2020 was awarded jointly to three researchers Harvey J. Alter, Charles M. Rice, and Michael Houghton for the discovery of Hepatitis C virus. Their works contributed to the isolation of the blood-borne virus, causing chronic hepatitis in 80% of infected person, resulting in cirrhosis, and in elevated risk of liver failure and hepatocellular carcinoma formation. Their results created the basis of HCV screening of blood, and blood products, achieving more than 95% cure of infected people without nearly side effects with direct-acting antiviral agents, supporting the goal of the WHO targeting the elimination of viral hepatitis by 2030.

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Section: Hepatitis C Virusmentioning

confidence: 99%

Section: Hepatitis C Virusmentioning

confidence: 99%

Section: Epidemiology and Clinical Signsmentioning

confidence: 99%

Section: Elimination Of Viral Hepatitis By 2030mentioning

confidence: 99%

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The Nobel Prize in Physiology or Medicine—2020

Hagymási

2021

Struct Chem

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“…HCV GT2 is greater in Asia and West Africa, whereas HCV GT4 infections are high in Central and Eastern Sub-Saharan Africa, North Africa, and the Middle East. HCV GTs 5, 6, and 7 are perhaps the most geographically limited, with GT5 accessible in South Africa and GT6 common in eastern and southeastern Asia, whereas GT7 also was stated in a small percentage of people in DR Congo (Coppola et al 2019;Rabaan et al 2019;Smith et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Computer-aided identification of a series of novel ligands showing high potency as hepatitis C virus NS3/4A protease inhibitors

et al. 2021

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Background Hepatitis C virus (HCV) is a global medical condition that causes several life-threatening chronic diseases in the liver. The conventional interferon-free treatment regimens are currently in use by a blend of direct-acting antiviral agents (DAAs) aiming at the viral NS3 protease. However, major concerns may be the issue of DAA-resistant HCV strains and the limited availability to the DAAs due to their high price. Due to this crisis, the developments of a new molecule with high potency as an NS3/4A protease inhibitor of the hepatitis-C virus remain a high priority for medical research. This study aimed to use in-silico methods to identify high potent molecule as an NS3/4A protease inhibitor and investigating the binding energy of the identified molecule in comparison with approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) through molecular docking. Results The model obtained by in-silico method have the following statistical records, coefficient of determination (r2) of 0.7704, cross-validation (q2LOO = 0.6914); external test set (r2(pred) = 0.7049) and Y-randomization assessment (cR2p = 0.7025). The results from the model were used to identify 12 new potential human HCV NS3/4A protease inhibitors, and it was observed that the identified molecule is well-fixed when docked with the receptor and was found to have the lowest binding energy of − 10.7, compared to approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) with − 9.5, − 10.0, − 10.5 binding energy, respectively. Conclusion The binding affinity (− 10.7) of the newly identified molecule docked with 3D structures of HCV NS3/4a protease/helicase (PDB ID: 4A92) was found to be better than that of Telaprevir, Simeprevir, and Voxilaprevir (approved direct-acting antiviral agents) which are − 9.5, − 10.0, and − 10.5, respectively. Hence, a novel molecule was identified showing high potency as HCV NS3/4a protease inhibitors.

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Sofosbuvir–velpatasvir in children 3–17 years old with hepatitis C virus infection

Jonas,

Romero,

Rosenthal

et al. 2024

J. pediatr. gastroenterol. nutr.

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BackgroundThe safety and efficacy of sofosbuvir–velpatasvir in children aged 3–17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated.MethodsIn this Phase 2, multicenter, open‐label study, patients received once daily for 12 weeks either sofosbuvir–velpatasvir 400/100 mg tablet (12–17 years), 200/50 mg low dose tablet or oral granules (3–11 years and ≥17 kg), or 150/37.5 mg oral granules (3–5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group.FindingsAmong 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3–5‐year‐olds, 93% (68/73) among 6–11‐year‐olds, and 95% (97/102) among 12–17‐year‐olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12–17‐year‐olds; vomiting, cough, and headache in 6–11‐year‐olds; and vomiting in 3–5‐year‐olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS‐331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight‐based dosing for children in this age range.InterpretationThe pangenotypic regimen of sofosbuvir–velpatasvir is highly effective and safe in treating children 3–17 years with chronic HCV infection.

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Overview of hepatitis C infection, molecular biology, and new treatment

Cited by 55 publications

References 143 publications

The Nobel Prize in Physiology or Medicine—2020

The Nobel Prize in Physiology or Medicine—2020

Computer-aided identification of a series of novel ligands showing high potency as hepatitis C virus NS3/4A protease inhibitors

Sofosbuvir–velpatasvir in children 3–17 years old with hepatitis C virus infection

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