Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include fever, dark urine, abdominal pain, and yellow tinged skin. The virus persists in the liver, becoming chronic, in about 70% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.
Hepatitis E is inflammation of the liver caused by infection with the hepatitis E virus (HEV); it is a type of viral hepatitis. Hepatitis E has mainly a fecal-oral transmission route that is similar to hepatitis A, although the viruses are unrelated. In retrospect, the earliest known epidemic of hepatitis E occurred in 1955 in New Delhi, but the virus was not isolated until 1983 by Russian scientists investigating an outbreak in Afghanistan. HEV is a positive-sense, single-stranded, nonenveloped, RNA icosahedral virus and one of five known human hepatitis viruses: A, B, C, D, and E.
Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Rimantadine can mitigate symptoms, including fever. Both rimantadine and the similar drug amantadine are derivates of adamantane. Rimantadine is found to be more effective than amantadine because when used the patient displays fewer symptoms. Rimantadine was approved by the Food and Drug Administration (FDA) in 1994.
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly and in-vitro assembly have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages. VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.
Taribavirin is an antiviral drug in Phase III human trials, but not yet approved for pharmaceutical use. It is a prodrug of ribavirin, active against a number of DNA and RNA viruses. Taribavirin has better liver-targeting than ribavirin, and has a shorter life in the body due to less penetration and storage in red blood cells. It is expected eventually to be the drug of choice for viral hepatitis syndromes in which ribavirin is active. These include hepatitis C and perhaps also hepatitis B and yellow fever.
In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word adiuvare, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."
Toll-like receptor 7, also known as TLR7, is a protein that in humans is encoded by the TLR7 gene. Orthologs are found in mammals and birds. It is a member of the toll-like receptor (TLR) family and detects single stranded RNA.
Toll-like receptor 8 is a protein that in humans is encoded by the TLR8 gene. TLR8 has also been designated as CD288. It is a member of the toll-like receptor (TLR) family.
Hepatitis B is an infectious disease caused by the Hepatitis B virus (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.
Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B.
Resiquimod (R-848) is a drug that acts as an immune response modifier, and has antiviral and antitumour activity. It is used as a topical gel in the treatment of skin lesions such as those caused by the herpes simplex virus and cutaneous T cell lymphoma, and as an adjuvant to increase the effectiveness of vaccines. In an animal disease model, systemic administration of resiquimod-loaded nanoparticles has been shown to improve response rates to cancer immunotherapy with a checkpoint inhibitor through stimulation of tumor-associated macrophages. It has several mechanisms of action, being both an agonist for toll-like receptor 7 and 8, and an upregulator of the opioid growth factor receptor. On 28 April 2016, orphan designation (EU/3/16/1653) was granted by the European Commission to Galderma R&D, France for resiquimod to be used in the treatment of cutaneous T-cell lymphoma.
Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK. The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication.
Galidesivir is an antiviral drug, an adenosine analog. It was developed by BioCryst Pharmaceuticals with funding from NIAID, originally intended as a treatment for hepatitis C, but subsequently developed as a potential treatment for deadly filovirus infections such as Ebola virus disease and Marburg virus disease, as well as Zika virus. Currently, galidesivir is under phase 1 human trial in Brazil for coronavirus.
A nucleoside-modified messenger RNA (modRNA) is a synthetic messenger RNA (mRNA) in which some nucleosides are replaced by other naturally modified nucleosides or by synthetic nucleoside analogues. modRNA is used to induce the production of a desired protein in certain cells. An important application is the development of mRNA vaccines, of which the first authorized were COVID-19 vaccines.
Vesatolimod (GS-9620) is an antiviral drug developed by Gilead Sciences, which acts as a potent and selective agonist of Toll-like receptor 7 (TLR7), a receptor involved in the regulation of the immune system. It is used to stimulate the immune system, which can increase its ability to combat chronic viral infections. Vesatolimod is in clinical trials to determine whether it is safe and effective in patients with Hepatitis B and HIV/AIDS, and has also shown activity against other viral diseases such as norovirus and enterovirus 71.
Bemnifosbuvir is an antiviral drug invented by Atea Pharmaceuticals and licensed to Roche for clinical development, a novel nucleotide analog prodrug originally developed for the treatment of hepatitis C. AT-527 is the orally bioavailable hemisulfate salt of AT-511, which is metabolised in several steps to the active nucleotide triphosphate AT-9010, acting as an RNA polymerase inhibitor and thereby interfering with viral replication. AT-527 has been researched for the treatment of coronavirus diseases such as that produced by SARS-CoV-2. It showed good results in early clinical trials but had inconsistent results at later stages, so the planned Phase 3 trials are being redesigned and results are not expected until late 2022.
