Antiviral candidates against the hepatitis E virus (HEV) and their combinations inhibit HEV growth in in vitro

Nishiyama, Takashi; Kobayashi, Tominari; Jirintai, Suljid; Nagashima, Shigeo; Primadharsini, Putu Prathiwi; Nishizawa, Tsutomu; Okamoto, Hiroaki

doi:10.1016/j.antiviral.2019.104570

Cited by 17 publications

(10 citation statements)

References 50 publications

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“…Ribavirin (HEV) and 2 -Cmethyladenosine (HCV) were included as inhibitors for the respective viruses. Of note, 2 -C-methyladenosine exhibited also anti-HEV properties, which is in line with findings from the literature [36]. HEV replication was significantly reduced after 72 and 96 h post transfection when compared to single transfection (Figure 1B, upper panels), while HCV replication was not affected (Figure 1B, lower panels).…”

Section: Hcv Impairs Hev Replication In Subgenomic Reporter Co-transf...supporting

confidence: 91%

Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems

Burkard

Proske

Resner

et al. 2022

Cells

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Background: Hepatitis C virus (HCV) constitutes a global health problem, while hepatitis E virus (HEV) is the major cause of acute viral hepatitis globally. HCV/HEV co-infections have been poorly characterized, as they are hampered by the lack of robust HEV cell culture systems. This study developed experimental models to study HCV/HEV co-infections and investigate viral interference in cells and humanized mice. Methods: We used state-of-the art human hepatocytes tissue culture models to assess HEV and HCV replication in co- or super-transfection settings. Findings were confirmed by co- and super-infection experiments in human hepatocytes and in vivo in human liver chimeric mice. Results: HEV was inhibited by concurrent HCV replication in human hepatocytes. This exclusion phenotype was linked to the protease activity of HCV. These findings were corroborated by the fact that in HEV on HCV super-infected mice, HEV viral loads were reduced in individual mice. Similarly, HCV on HEV super-infected mice showed reduced HCV viral loads. Conclusion: Direct interference of both viruses with HCV NS3/4A as the determinant was observed. In vivo, we detected reduced replication of both viruses after super-infection in individual mice. These findings provide new insights into the pathogenesis of HCV-HEV co-infections and should contribute to its clinical management in the future.

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Section: Hcv Impairs Hev Replication In Subgenomic Reporter Co-transf...supporting

confidence: 91%

Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems

Burkard

Proske

Resner

et al. 2022

Cells

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“…Several clinical studies have shown a continued virological response in patients with a 3 – 6-months course of ribavirin monotherapy ( Lhomme, 2019 , Pischke, 2013 ). Also, in vitro studies have revealed the ability of ribavirin to inhibit the growth of HEV ( Nishiyama, 2019 ).…”

Section: Treatment Of Chronic Hev Infectionmentioning

confidence: 99%

“…Nevertheless, treatment can be extended up to 12 months in case of non-response ( Kamar, 2016 ). Also, combination therapy of interferon and ribavirin can be used for treating chronic HEV infection ( Nishiyama, 2019 , Netzler, 2019 ). However, interferon is known to have substantial adverse effects and graft rejection in transplant recipients.…”

Section: Treatment Of Chronic Hev Infectionmentioning

confidence: 99%

Hepatitis E Virus: An emerging enigmatic and underestimated pathogen

Raji

Ooi

Taib

et al. 2022

Saudi Journal of Biological Sciences

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Hepatitis E virus (HEV) is an RNA virus causing hepatitis E disease. The virus is of one serotype but has diverse genotypes infecting both humans and animals. Based on evidence from seroprevalence studies, about 2 billion people are estimated to have been infected with HEV globally. HEV, therefore, poses a significant public health and economic challenge worldwide. HEV was discovered in the 1980s and was traced back to the 1955 – 1956 outbreak of hepatitis that occurred in India. Subsequently, several HEV epidemics involving thousands of individuals have occurred nearly annually in different countries in Asia and Africa. Initially, the virus was thought to be only enterically transmitted, and endemic in developing countries. Due to the environmental hygiene and sanitation challenges in those parts of the world. However, recent studies have suggested otherwise with the report of autochthonous cases in industrialised countries with no history of travel to the so-called endemic countries. Thus, suggesting that HEV has a global distribution with endemicity in both developing and industrialised nations. Studies have also revealed that HEV has multiple risk factors, and modes of transmission as well as zoonotic potentials. Additionally, recent findings have shown that HEV leads to severe disease, particularly among pregnant women. In contrast to the previous narration of a strictly mild and self-limiting infection. Studies have likewise demonstrated chronic HEV infection among immunocompromised persons. Consequent to these recent discoveries, this pathogen is considered a re – emerging virus, particularly in the developed nations. However, despite the growing public health challenges of this pathogen, the burden is still underestimated. The underestimation is often attributed to poor awareness among clinicians and a lack of routine checks for the disease in the hospitals. Thus, leading to misdiagnosis and underdiagnosis. Hence, this review provides a concise overview of epidemiology, diagnosis, and prevention of hepatitis E.

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“…Nishiyama et al[ 143 ] reported a promising compound, 2'-C-methylguanosine, that suppressed the growth of HEV3 in cell cultures and showed in vitro synergistic interaction with ribavirin against the HEV. However, there is no study yet exploring its efficacy and safety in animal models and human trials.…”

Section: Promising Treatment Options For Ribavirin-resistant Hev Infementioning

confidence: 99%

Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment

Aslan

Balaban

2020

WJG

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The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients ( e.g ., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.

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Antiviral candidates against the hepatitis E virus (HEV) and their combinations inhibit HEV growth in in vitro

Cited by 17 publications

References 50 publications

Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems

Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems

Hepatitis E Virus: An emerging enigmatic and underestimated pathogen

Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment

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