Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin itching and skin rash. Recovery generally takes two to seven days. In a small proportion of cases, the disease develops into a more severe dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.
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 viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural viricides are produced by some plants such as eucalyptus and Australian tea trees.
The hepatitis C virus (HCV) is a small, enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer and lymphomas in humans.
Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes of the virus have been found, and a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, scientists' understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.
Tenofovir disoproxil, sold under the trade name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure. It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir, and elvitegravir/cobicistat/emtricitabine/tenofovir. It does not cure HIV/AIDS or hepatitis B. It is available by mouth as a tablet or powder.
Cidofovir, brand name Vistide, is a topical or injectable antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis in people with AIDS.
Clioquinol (iodochlorhydroxyquin) is an antifungal drug and antiprotozoal drug. It is neurotoxic in large doses. It is a member of a family of drugs called hydroxyquinolines which inhibit certain enzymes related to DNA replication. The drugs have been found to have activity against both viral and protozoal infections.
Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, or immunological imprinting, is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a second slightly different version of that foreign pathogen is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections. Antibodies or T-cells induced during infections with the first variant of the pathogen are subject to repertoire freeze, a form of original antigenic sin.
Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections.
Orthopoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and monkeypox. The most widely known member of the genus is Variola virus, which causes smallpox. It was eradicated globally by 1977, through the use of Vaccinia virus as a vaccine. The most recently described species is the Alaskapox virus, first isolated in 2015.
RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases, which all organisms use to catalyze the transcription of RNA from a DNA template.
Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.
PSI-6130 is an experimental treatment for hepatitis C. PSI-6130 is a member of a class of antiviral drugs known as nucleoside polymerase inhibitors that was created by chemist Jeremy L. Clark. Specifically, PSI-6130 inhibits the hepatitis C virus RNA dependant RNA polymerase called NS5B.
Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.
Favipiravir, sold under the brand name Avigan among others, is an antiviral medication used to treat influenza in Japan. It is also being studied to treat a number of other viral infections, including SARS-CoV-2. Like the experimental antiviral drugs T-1105 and T-1106, it is a pyrazinecarboxamide derivative.
ERDRP-0519 is an antiviral drug which is the first drug specifically developed to target the measles morbillivirus. It acts as an inhibitor of the viral enzyme RNA polymerase which is essential for viral replication, and in animal studies showed good oral bioavailability and protected ferrets from otherwise lethal doses of a morbillivirus when administered up to three days after infection.
MK-608 is an antiviral drug, an adenosine analog. It was originally developed by Merck & Co. as a treatment for hepatitis C, but despite promising results in animal studies, it was ultimately unsuccessful in clinical trials. Subsequently it has been widely used in antiviral research and has shown activity against a range of viruses, including Dengue fever, tick-borne encephalitis virus, poliovirus, and most recently Zika virus, in both in vitro and animal models. Since it has already failed in human clinical trials previously, it is unlikely MK-608 itself will be developed as an antiviral medication, but the continuing lack of treatment options for these emerging viral diseases means that much research continues using MK-608 and related antiviral drugs.
NITD008 is an antiviral drug classified as an adenosine analog. It was developed as a potential treatment for flavivirus infections and shows broad spectrum antiviral activity against many related viruses such as dengue virus, West Nile virus, yellow fever virus, Powassan virus, hepatitis C virus, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus, and Zika virus. However, NITD008 proved too toxic in pre-clinical animal testing to be suitable for human trials, but it continues to be used in research to find improved treatments for emerging viral diseases.
Non-structural protein 5B (NS5B) inhibitors are a class of direct-acting antivirals widely used in the treatment of chronic hepatitis C. Depending on site of action and chemical composition, NS5B inhibitors may be categorized into three classes—nucleoside active site inhibitors (NIs), non-nucleoside allosteric inhibitors, and pyrophosphate analogues. Subsequently, all three classes are then subclassified. All inhibit RNA synthesis by NS5B but at different stages/sites resulting in inability of viral RNA replication. Expression of direct-acting NS5B inhibitors does not take place in cells that are not infected by hepatitis C virus, which seems to be beneficial for this class of drugs.
Broad-spectrum antivirals (BSAs) are a class of molecules or compounds, which inhibit the replication of a broad range of viruses. BSAs could be divided into experimental and investigational agents, and approved drugs. BSAs work by inhibiting viral proteins or by targeting host cell factors and processes exploited by different viruses during infection. As of 2021, there are 150 known BSAs in varying stages of development, effective against 78 human viruses. BSAs are potential candidates for treatment of emerging and re-emerging viruses, such as ebola, marburg, and SARS-CoV-2. Many BSAs show antiviral activity against other viruses than originally investigated. Efforts in drug repurposing for SARS-CoV-2 is currently underway. A database of BSAs and viruses they inhibit could be found here.
