I started writing on the Pharmacology of antivirals in my last post, and we were able to discuss the treatments for HIV, drug mechanisms, actions, and side effects of the drugs. In that post, I explained how HIV gets into the host cell by utilizing special proteins GP41, and GP120 to bind with the host cell's receptors CD4 proteins, and the (CCR5 and CXCR4), and how Nucleoside Reverse Transcriptase Inhibitors can be used to inhibit reverse transcriptase enzymes, thereby preventing the virus from converting the cell's RNA to DNA which prevents the cell replication. I also discussed other drugs which have different functions such as Non-nucleotide Reverse Transcriptase Inhibitors, Integrase inhibitor drugs, and Protease inhibitor drugs. If you missed the post, you can read it by clicking on Pharmacology || HIV Antiviral Drug Mechanism of Action and Side Effect. Today, we are going to continue on the pharmacology and antivirals, and today we will be talking about Influenza medications, and we could touch on herpes, and hepatitis medication. Let's begin without taking any more of your time.
Influenza is basically that respiratory disease you refer to as flu. I shouldn't be doing this but for easy understanding, it is caused by the influenza virus. It is primarily contracted through respiratory droplets, and they get into the respiratory system. In the human body, the virus RNA gets into the host cell structure, so it can be able to reproduce more virus cells. When it gets into the respiratory tract, it binds to the cells of the respiratory tract. The Influenza virus possesses RNA, Hemagglutinin, neuraminidases, and M2 proton channels. The Hemagglutinin of the influenza virus binds with proteins in the respiratory tract known as the sialic acid proteins though the process of receptor-mediated endocytosis allowing the virus enters into the cell. In the cell, the M2 proton channels allow for protons to enter into the viral structure, acidifying the environment, and allowing for the process of uncoating the viral RNA of the cell which will be taken into the nucleus of the host cell. ,. In the host nucleus, the viral RNA utilizes the 5'cap present in the host cell's mRNA through endonuclease. The viral RNA needs the 5'cap because it doesn't possess it but the host mRNA does, and it is needed to bind with the cell ribosomes. The influenza viral RNA leaves the nucleus and goes to the host cell ribosome where it utilizes the proteins in the ribosome and makes more viral RNA through the host cell RNA polymerase and takes them to the Golgi Apparatus where they utilized with the viral proteins to create new viruses. The Golgi Apparatus where the viruses are fuses to the cell membrane where they are expelled but are still stuck to the sialic acid with the help of the Hemagglutinin protein of the virus. For the virus to be completely free from the cell and infect other cells, the neuraminidase protein of the virus cut the attachment between the host cell and the virus. ,,.
With influenza viral drugs, every step can be inhibited. The first process of influenza uncoating can be inhibited by preventing the ions from getting into the endosome of the cells thereby preventing the release of the viral RNA into the endosome. Drugs such as Amantadine inhibit the process, and it is used for the treatment of Influenza A.. If the virus already got into the nucleus of the cell, the next thing is for the endonuclease to transfer the 5'cap from the mRNA in the nucleus of the host to the virus RNA, helping the virus to have the 5'cap in its cell allowing it to be able to bind to the cell ribosome. Inhibiting the endonuclease activity is another way to prevent the virus from getting the 5'cap, and preventing the binding with the ribosome preventing protein synthesis. For these to happen, drugs such as Baloxavir are used to inhibit the endonuclease, and it can be used for influenza type A and B, and it is used for patients within 48 hours of symptom onset used to prevent the severity. ,.
If the influenza virus is able to pass through the nucleus and has been able to get the 5'cap, then another way to threat is by inhibiting Neuraminidase. Using neuraminidase inhibitors will prevent the new viral cells from cutting off the sialic acid protein and infecting other cells. Drugs such as Oseltamivir, and Zanamivir which are used in treating influenza types A and B, it can also be used as a prophylaxis, and giving within 48 hours of symptom onset.,.
Taking these medications also come with adverse effects and there are contradictions also. While most of the drugs for influenza are usually good boys, drugs like Amantadine can cause side effects such as livedo reticularis (skin manifestations, characterized by a mottled discoloration of the skin, typically on the legs and trunk), ataxia (difficulty with coordination and balance), as well as prolong QT intervals in the heart.,
Conclusion
While these drugs work to treat the virus, they start with reducing the symptoms at first. Before I go, let me quickly say that the Flu you often say when you refer to bacterial infection giving flu-like symptoms is wrong. Flu is caused by a virus and not bacteria, although bacterial pneumonia can cause flu-like symptoms, it is not flu. Thanks a lot for reading this post, our pharmacology series continue and we are still on viral Pharmacology. In my next post, we will look at other viruses and their drugs.
Image Reference
Image 1 || Flickr || 3D visualisation of influenza virus