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World Journal of Gastroenterology Oct 2020The 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... (Review)
Review
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 (., 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.
Topics: Aged; Aged, 80 and over; Animals; Antiviral Agents; Female; Hepatitis E; Hepatitis E virus; Hepatitis, Chronic; Humans; Pregnancy; Ribavirin; Swine
PubMed: 33071523
DOI: 10.3748/wjg.v26.i37.5543 -
Viruses Apr 2021The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute... (Review)
Review
The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.
Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antiviral Agents; Hemorrhagic Fever, Ebola; Humans; Middle East Respiratory Syndrome Coronavirus; Mutagenesis; Nucleosides; Pyrazines; Ribavirin; SARS-CoV-2; Virus Replication; Zika Virus; Zika Virus Infection; COVID-19 Drug Treatment
PubMed: 33924302
DOI: 10.3390/v13040667 -
Cells Jan 2022Alterations of methionine cycle in steatohepatitis, cirrhosis, and hepatocellular carcinoma induce MAT1A decrease and MAT2A increase expressions with the consequent... (Review)
Review
Alterations of methionine cycle in steatohepatitis, cirrhosis, and hepatocellular carcinoma induce MAT1A decrease and MAT2A increase expressions with the consequent decrease of S-adenosyl-L-methionine (SAM). This causes non-alcoholic fatty liver disease (NAFLD). SAM administration antagonizes pathological conditions, including galactosamine, acetaminophen, and ethanol intoxications, characterized by decreased intracellular SAM. Positive therapeutic effects of SAM/vitamin E or SAM/ursodeoxycholic acid in animal models with NAFLD and intrahepatic cholestasis were not confirmed in humans. In in vitro experiments, SAM and betaine potentiate PegIFN-alpha-2a/2b plus ribavirin antiviral effects. SAM plus betaine improves early viral kinetics and increases interferon-stimulated gene expression in patients with viral hepatitis non-responders to pegIFNα/ribavirin. SAM prevents hepatic cirrhosis, induced by CCl4, inhibits experimental tumors growth and is proapoptotic for hepatocellular carcinoma and MCF-7 breast cancer cells. SAM plus Decitabine arrest cancer growth and potentiate doxorubicin effects on breast, head, and neck cancers. Furthermore, SAM enhances the antitumor effect of gemcitabine against pancreatic cancer cells, inhibits growth of human prostate cancer PC-3, colorectal cancer, and osteosarcoma LM-7 and MG-63 cell lines; increases genomic stability of SW480 cells. SAM reduces colorectal cancer progression and inhibits the proliferation of preneoplastic rat liver cells in vivo. The discrepancy between positive results of SAM treatment of experimental tumors and modest effects against human disease may depend on more advanced human disease stage at moment of diagnosis.
Topics: Animals; Antiviral Agents; Betaine; Carcinogenesis; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Colorectal Neoplasms; Humans; Liver Neoplasms; Male; Methionine Adenosyltransferase; Non-alcoholic Fatty Liver Disease; Rats; Ribavirin; S-Adenosylmethionine
PubMed: 35159219
DOI: 10.3390/cells11030409 -
Viruses Jul 2019Hantaviruses, members of the order , family , have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of... (Review)
Review
Hantaviruses, members of the order , family , have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of disease associated with hantavirus infection include hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). There are currently no FDA-approved vaccines or treatments for these hantavirus diseases. This review provides a summary of the status of vaccine and antiviral treatment efforts including those tested in animal models or human clinical trials.
Topics: Adrenal Cortex Hormones; Amides; Animals; Antiviral Agents; Clinical Trials as Topic; Orthohantavirus; Hantavirus Infections; Hantavirus Pulmonary Syndrome; Hemorrhagic Fever with Renal Syndrome; Humans; Immunotherapy; Lactoferrin; Models, Animal; Nucleosides; Piperidines; Pyrazines; Quinazolines; Recombinant Proteins; Ribavirin; Triazoles; Vaccines, Synthetic; Viral Vaccines
PubMed: 31277410
DOI: 10.3390/v11070610 -
Viruses Jun 2021Mammarenaviruses are prevalent pathogens distributed worldwide, and several strains cause severe cases of human infections with high morbidity and significant mortality.... (Review)
Review
Mammarenaviruses are prevalent pathogens distributed worldwide, and several strains cause severe cases of human infections with high morbidity and significant mortality. Currently, there is no FDA-approved antiviral drugs and vaccines against mammarenavirus and the potential treatment option is limited to an off-label use of ribavirin that shows only partial protective effect and associates with side effects. For the past few decades, extensive research has reported potential anti-mammarenaviral drugs and their mechanisms of action in host as well as vaccine candidates. This review describes current knowledge about mammarenavirus virology, progress of antiviral drug development, and technical strategies of drug screening.
Topics: A549 Cells; Animals; Antiviral Agents; Arenaviridae; Chlorocebus aethiops; Clinical Trials as Topic; Drug Development; Drug Repositioning; HEK293 Cells; High-Throughput Screening Assays; Humans; Ribavirin; Vero Cells; Virus Replication
PubMed: 34206216
DOI: 10.3390/v13071187 -
Clinical Infectious Diseases : An... Jul 2022Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD)... (Meta-Analysis)
Meta-Analysis
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies.
BACKGROUND
Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin.
METHODS
Relevant databases were queried and study outcomes extracted using a standardized method and summarized.
RESULTS
Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0-3%), but CLAD progression 180-360 days postinfection was substantial (pooled incidences 19-24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27-1.18]), although results were highly variable between studies.
CONCLUSIONS
RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
Topics: Humans; Lung; Metapneumovirus; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Paramyxoviridae Infections; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Ribavirin; Transplant Recipients
PubMed: 35022697
DOI: 10.1093/cid/ciab969 -
Antimicrobial Agents and Chemotherapy Aug 2020The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted the repurposing of drugs on the... (Review)
Review
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted the repurposing of drugs on the basis of promising and therapeutic results with other human coronavirus diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir-ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized, controlled trials are showing poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Administration Schedule; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; Ribavirin; Ritonavir; SARS-CoV-2; Survival Analysis; Treatment Outcome
PubMed: 32631826
DOI: 10.1128/AAC.01101-20 -
Cureus May 2021Lassa fever (LF) is on the top-priority infections list of both the Food and Drug Administration (FDA) and World Health Organization (WHO). This review explores the... (Review)
Review
Lassa fever (LF) is on the top-priority infections list of both the Food and Drug Administration (FDA) and World Health Organization (WHO). This review explores the different treatment approaches found in the literature within the last 20 years. Even though ribavirin stands out among medication options, only one clinical trial was done to assess its efficacy in humans, which necessitated that we look in-depth about the latest updates in managing LF infection. For that matter, we used a Medical Subject Headings (MeSH) search on PubMed. Inclusion criteria included papers written in the English language and human subjects. Intravenous (IV) ribavirin is the most effective treatment for an acute infection. Post-exposure prophylaxis with oral ribavirin is recommended. There is not sufficient evidence to recommended convalescent plasma for the treatment of Lassa fever. LF continues to be left in the shade from global and scientific attention despite experts expecting a rise in current and future infections due to the Lassa fever virus (LFV).
PubMed: 34094756
DOI: 10.7759/cureus.14797 -
Viruses Jul 2019Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is... (Review)
Review
Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible.
Topics: Animals; Antiviral Agents; Chronic Disease; Female; Genotype; Hepatitis E; Hepatitis E virus; Humans; Immunocompromised Host; Pregnancy; Pregnancy Complications, Infectious; Ribavirin
PubMed: 31284447
DOI: 10.3390/v11070617