The discovery of viruses in the late 19th century marked the beginning of the search for treatments against these microscopic pathogens. Early progress was slow as scientists worked to understand viral replication cycles and identify potential antiviral targets. A major breakthrough came in the 1940s with the development of Idarubicin, one of the first drugs shown to inhibit a viral enzyme called reverse transcriptase in retroviruses like HIV. However, it wasn’t until the 1960s that the first approved antiviral medications arrived with the launch of Amantadine for influenza A virus. Further advancements in virology and molecular biology during the late 20th century rapidly accelerated antiviral drug discovery. Today, antivirals target various stages of the viral life cycle like entry, replication, assembly and release. With new viruses continually emerging as public health threats, the quest continues for versatile antiviral platforms applicable across diverse families.
There are several classes of antiviral drugs that work in different ways to combat viral infections. Some of the major types include:
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
NRTIs work by interfering with the reverse transcriptase enzyme that some viruses like HIV and hepatitis B need to replicate. By mimicking the nucleotide building blocks of DNA, NRTIs are incorporated into the growing DNA chain, but don't form a complete DNA strand, stopping viral replication in its tracks. Well-known NRTIs include zidovudine (AZT), didanosine (Videx), lamivudine (3TC), emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF, Viread).
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
NNRTIs inhibit reverse transcriptase through a different mechanism than NRTIs. They bind directly to reverse transcriptase and disable its function without being incorporated into the DNA chain. Examples include efavirenz (Sustiva), etravirine (Intelence) and rilpivirine (Edurant). These are commonly used in combination with NRTIs.
Protease Inhibitors (PIs)
PIs prevent viruses like HIV from producing functional proteins by inhibiting the protease enzyme they use to process immature viral proteins into mature proteins. Some widely used PIs are indinavir (Crixivan), saquinavir (Invirase), ritonavir (Norvir), lopinavir/ritonavir (Kaletra) and darunavir (Prezista).
Entry and Fusion Inhibitors
Rather than blocking viral replication after entry into cells, entry/fusion inhibitors stop viruses from entering cells in the first place by interfering with proteins involved in attachment and entry. Maraviroc (Selzentry) blocks HIV entry, while enfuvirtide (Fuzeon) inhibits fusion.
Targeting the Viral Genome
Some newer Antiviral Drugs work by targeting the viral genome directly. Hepatitis C protease inhibitors simeprevir (Olysio) and sofosbuvir (Sovaldi) work against hepatitis C virus replication by attacking its non-human genome.
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