Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.
Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.
Cidofovir, brand name Vistide, is a topical or injectable antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis in people with AIDS.
Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs.
Spermine is a polyamine involved in cellular metabolism that is found in all eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some bacteria as well. It is found as a polycation at physiological pH. Spermine is associated with nucleic acids and is thought to stabilize helical structure, particularly in viruses.
Glycosyltransferases are enzymes that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar to a nucleophilic glycosyl acceptor molecule, the nucleophile of which can be oxygen- carbon-, nitrogen-, or sulfur-based.
Moronic acid is a natural triterpene. Moronic acid can be extracted from Rhus javanica, a sumac plant traditionally believed to hold medicinal applications. The molecule has also been extracted from mistletoe.
Sanicula europaea, the sanicle or wood sanicle, is a perennial plant of the family Apiaceae.
NS2-3 protease is an enzyme responsible for proteolytic cleavage between NS2 and NS3, which are non-structural proteins that form part of the HCV virus particle. NS3 protease of hepatitis C virus, on the other hand, is responsible for the cleavage of non-structural protein downstream. Both of these proteases are directly involved in HCV genome replication, that is, during the viral life-cycle that leads to virus multiplication in the host that has been infected by the virus.
Tetrandrine, a bis-benzylisoquinoline alkaloid, is a calcium channel blocker. It is isolated from the plant Stephania tetrandra, and other Chinese and Japanese herbs.
Hepatitis B virus DNA polymerase is a hepatitis B viral protein. It is a DNA polymerase that can use either DNA or RNA templates and a ribonuclease H that cuts RNA in the duplex. Both functions are supplied by the reverse transcriptase (RT) domain.
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.
The first human immunodeficiency virus (HIV) case was reported in the United States in the early 1980s. Many drugs have been discovered to treat the disease but mutations in the virus and resistance to the drugs make development difficult. Integrase is a viral enzyme that integrates retroviral DNA into the host cell genome. Integrase inhibitors are a new class of drugs used in the treatment of HIV. The first integrase inhibitor, raltegravir, was approved in 2007 and other drugs were in clinical trials in 2011.
Simeprevir, sold under the trade names Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.
3-Deazaneplanocin A is a drug which acts as both a S-adenosylhomocysteine synthesis inhibitor and also a histone methyltransferase EZH2 inhibitor. Studies have shown that it has in vitro against a variety of different tumor cell lines.
Carbocyclic nucleosides are nucleoside analogues in which a methylene group has replaced the oxygen atom of the furanose ring. These analogues have the nucleobase attached at a simple alkyl carbon rather than being part of a hemiaminal ether linkage. As a result, they have increased chemical stability. They also have increased metabolic stability because they are unaffected by phosphorylases and hydrolases that cleave the glycosidic bond between the nucleobase and furanose ring of nucleosides. They retain many of the biological properties of the original nucleosides with respect to recognition by various enzymes and receptors.
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.
EICAR is a drug which acts as an inhibitor of the enzyme IMP dehydrogenase. It is a nucleoside derivative which has both anti-cancer and antiviral effects, and was originally developed for the treatment of leukemia, but was unsuccessful in human clinical trials. It has broad spectrum antiviral effects with activity against pox viruses, Semliki forest virus, Junin virus, reovirus, influenza, measles virus and respiratory syncytial virus among others, although it is not active against coronaviridae such as SARS-CoV-1. This useful spectrum of activity means that EICAR and related derivatives continue to be investigated for the treatment of viral diseases.
Merimepodib (VX-497) is a drug which acts as an inhibitor of the enzyme inosine monophosphate dehydrogenase, which is required for the synthesis of nucleotide bases containing guanine. This consequently inhibits synthesis of DNA and RNA, and results in antiviral and immunosuppressive effects. It progressed as far as Phase 2b human clinical trials against Hepatitis C but showed only modest benefits in comparison to existing treatments, however it continues to be researched, and also shows activity against other viral diseases such as Zika virus and foot and mouth disease virus.
S416 (GTPL-11164) is a drug which acts as a selective inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme is involved in the synthesis of pyrimidine nucleosides in the body, which are required for the synthesis of DNA and RNA. This is an important rate-limiting step in the replication of viruses, and so DHODH inhibitors may have applications as broad-spectrum antiviral drugs. In tests in vitro, S416 was found to have antiviral activity against a range of pathogenic RNA viruses including influenza, Zika virus, Ebola virus and SARS-CoV-2.
