2 ', 3' - dideoxynucleosides (ddNs)

2 ', 3' - dideoxynucleosides (ddNs) are a class of small molecule nucleoside analogues with special structures and significant antiviral activity.

Molecular structure

In ddNs molecules, pentacyclic sugars linked to nitrogen heterocyclic bases do not have hydroxyl groups at the second and third carbon atoms. According to its structure, dNs can be further divided into four categories. One is a ddNs molecule that is replaced by other functional groups at positions 2 'and 3', the second is a ddNs molecule that has no other functional groups at positions 2 'and 3', the third is 2 ', 3' - dideoxy-2 ', 3' - dihydronucleosides (d4Ns), and the fourth is another type of ddNs molecule. Among them, the second type of ddNs molecules are the most widely used.

Antiviral mechanism

DDNs can generate antiviral activity in three main ways. One is by inhibiting the activity of enzymes required for viral nucleic acid replication. The second method involves inhibiting the activity of mRNA translation and blocking as well as RNA insertion enzymes involved in the virus. The third is to directly block the synthesis of viral DNA.

Antiviral drugs

AIDS is caused by human immunodeficiency virus (HIV). Since the first case of AIDS appeared in the 1980s, a large number of AIDS patients around the world have been diagnosed. Therefore, the development of anti AIDS drugs is extremely urgent. Since patients infected with AIDS virus are usually sensitive to other viruses (such as herpes simplex virus, cytomegalovirus, varicella zoster virus, etc.), the research and development of other antiviral drugs have also been promoted.

In the research of anti HIV, it is the first time to find that dideoxynucleosides can inhibit reverse transcriptase and stop the extension of DNA chain, thus inhibiting the replication of HIV. Subsequently, it was found that dideoxynucleoside compounds can also block the extension of HBV DNA chains, thereby achieving the effect of inhibiting HBV replication.

Some ddNs with antiviral activity have been clinically used as anti HIV or anti hepatitis B drugs. DdNs have low toxicity and certain antiviral effects. Clinically, it can be used for oral treatment of viral diseases. In addition, some ddNs can also be used for local treatment. At present, the ddNs used clinically mainly include zidovudine (AZT), zalcitabine (DDC), stavudine (D4T), lamivudine (3TC), abacavir (ABC), etc.