Pharmacology || HIV Antiviral Drug Mechanism of Action and Side Effect

One virus that a lot of us are familiar with is the HIV virus, so I will be discussing first antiretroviral therapies which are the first category against HIV. Retroviruses convert RNA to DNA, they usually attack the immune system which are the T-helper cells which are CD4-positive cells. When HIV gets into the body, it utilizes special proteins which include GP41, and GP120, to bind with host cell receptors which are CD4 proteins and the (CCR5 and CXCR4) and enter into the host cells. In other to prevent the HIV virus from entering into the patient's immune cells, certain drugs can be used to prevent its fusion, these drugs include Enfuvirtide which inhibits entry of the virus into the host cell by inhibiting the interaction between the GP41 of the virus and the CD4 protein of the cell, Maraviroc is another drug that prevents the virus from entering into the cell by inhibiting the GP120 from binding to the CCR5 protein receptor.,,,,.

This is for cases when the virus RNA hasn't entered the host cell. When the virus has entered the host cell, it releases its RNA as well as releasing the Reverse Transcriptase enzyme which converts RNA into DNA, thereby allowing the virus to have DNA that can be transcribed into the host T-helper cell's DNA. In this process, it is good to get drugs that can inhibit the enzyme Reverse Transcriptase which is responsible for converting the RNA to DNA, which will enable the virus to replicate. There are numerous drugs that can be used to inhibit reverse transcriptase enzymes but they can be divided into two groups. The main category is Nucleoside Reverse Transcriptase Inhibitors (NRTIs). For the enzyme to do this, it needs to be able to use the nucleotides around the host's cells to rewrite the RNA cells making viral DNA from the host's DNA but with drugs such as Nucleoside Reverse Transcriptase Inhibitors (NRTIs), the Reverse transcriptase enzyme of the virus misread the drug for the DNA nucleotide causing it to add it to its chain which will prevent further addition of nucleotides into the chain since the Nucleoside Reverse Transcriptase Inhibitors (NRTIs) prevents any further addition of host DNA nucleotide into the chain. These Nucleoside Reverse Transcriptase Inhibitors (NRTIs) drugs include Zidovudine, Abacavir, Stavudine, Lamivudine, Tenofovir, and Didanosine. ,,,.

The other drug group is the Non-nucleotide Reverse Transcriptase Inhibitors (NNRTIs). While the Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are being picked into the chain, Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) bind to the allosteric site of the enzyme itself, changing the shape of the enzyme, thereby preventing the reading of the RNA and the nearby nucleotides, thereby preventing the creation of a new viral DNA. The drug in the group includes Nevirapine, Efavirenz, Etravirine, and Delavirdine.,. If the viral DNA gets taken up into the host cell nucleus the viral enzyme known as integrase cuts into the host DNA and infuses the viral DNA into the host cell's DNA. when the viral DNA has entered into the nucleus of the host cell, certain drugs can be used to prevent the integrase enzyme from performing its function. This category of drug is known as an Integrase inhibitor which prevents the enzyme integrase from performing its function. The drugs in this group are Dolutegravir, Raltegravir, and Elvitegravir.,.

The viral DNA if successfully transcribed into host cell DNA, would create viral RNA which will bind to ribosomes in the cytoplasm of the cell to start the process of translation, and then start to make polyproteins which will be broken down by protease, to create other structural and functional proteins. for the replication of more viruses. If the enzyme protease is inhibited, it would prevent the ability cleaving of the transcripted polyprotein. There are a lot of drugs in the group Protease inhibitors, which inhibit protease from cleaving to the polyproteins. The drugs include Darunavir, Atazanavir, Indinavir, nelfinavir, and Tipranavir. ,,,,. If the viral RNA gets taken up into the Golgi apparatus, alongside the proteins, then the RNA will be infused into the virus and sent to the cell membrane where it is exocytosed into the vascular system to infect other cells in the body. Using the Highly active antiretroviral therapy (HAART) regimen is a good way to prevent this action. This is possible by using 2 drugs from the NRTIs, and another drug group such as the NNRTIs, an Integrase inhibitor, or a protease inhibitor to prevent the action of exocytosing the virus in the system. This will prevent the viral load in the system. The HAART can be used alongside adjuncts such as the Fusion/entry inhibitors (Enfurvitide, and maraviroc).,,.

Using these medications can help prevent the virus from continuously replicating, thereby reducing the viral load, but they come with adverse effects. In the case of Nucleoside Reverse Transcriptase Inhibitors (NRTIs), it can lead to mitochondrial toxicity, thereby causing the lack of ATP which can cause patients who are being treated with this class of drug to suffer from myopathy, altered peripheral neuron causing peripheral neuropathy, hepatic steatosis as a result of fatty acid build-up, and lactic acidosis.,,. It can lead to pancreatitis as a result of affecting the pancreas. Drugs such as Stavudine can induce this.,. Using NRTIs can lead to nephrotoxicity which can cause kidney injuries., It can also lead to anemia, hypersensitivity which would cause nausea, vomiting, diarrhea, rash, and fever.,. Non-nucleotide Reverse Transcriptase Inhibitors (NNRTIs) drugs can cause adverse effects such as hepatotoxicity, it can lead to central nervous system toxicity, and teratogenic effects.. Integrase inhibitor drugs can cause rhabdomyolysis . With protease inhibitors, side effects can include crystal-induced nephropathy, lipodystrophy, and hyperglycemia. ,.

Conclusion

In this post, I was able to explain the antiviral drug groups and mechanism of action for the HIV virus. In my next post, I will be writing about influenza, Hepatitis, and Herpes medications.

Image Reference
Image 1 || Wikimedia Commons || Antiretroviral Drugs to Treat HIV Infection

Image 2|| Wikimedia Commons || HIV-drug-classes