Antivirals Flashcards
Viral Neuraminidase Inhibitors
Viral neuraminidase inhibitors are a class of drugs that target the enzyme neuraminidase, which is found on the surface of some viruses such as influenza. This enzyme is essential for the release and spread of viruses from infected cells to other cells in the body.
When a neuraminidase inhibitor is administered to an infected individual, it binds to the neuraminidase enzyme and prevents it from functioning properly. This reduces the ability of the virus to spread to other cells and therefore limits the severity and duration of the infection.
The most commonly used viral neuraminidase inhibitors are oseltamivir (Tamiflu) and zanamivir (Relenza), which are used to treat and prevent influenza A and B infections. These drugs are most effective when taken within 48 hours of the onset of symptoms.
Mode of action of Acyclovir
Acyclovir is an antiviral drug that is used to treat infections caused by the herpes simplex virus (HSV), including genital herpes and cold sores, as well as the varicella-zoster virus, which causes chickenpox and shingles.
The mode of action of acyclovir involves its ability to inhibit viral DNA synthesis. Once inside the infected cell, acyclovir is converted into its active form, acyclovir triphosphate, by the viral enzyme thymidine kinase.
Acyclovir triphosphate then works by inhibiting the viral DNA polymerase enzyme, which is necessary for the replication of the virus. Specifically, acyclovir triphosphate competes with deoxyguanosine triphosphate (dGTP) for binding to the viral DNA polymerase, which results in the incorporation of acyclovir into the growing viral DNA chain instead of dGTP.
This incorporation of acyclovir into the viral DNA chain causes premature chain termination, which effectively halts the replication of the virus. As a result, the viral load is reduced, and symptoms of the infection are alleviated.
Describe Acyclovir prodrugs
However, acyclovir has poor oral bioavailability due to its low solubility and low membrane permeability, which limits its effectiveness as a treatment.
There are several acyclovir prodrugs that have been developed, including valacyclovir, famciclovir, and penciclovir. Valacyclovir is an oral prodrug of acyclovir that is rapidly converted into acyclovir in the body by the enzyme valacyclovir hydrolase. Famciclovir is another oral prodrug of acyclovir that is metabolized into penciclovir, which is then converted into acyclovir by viral thymidine kinase.
The advantage of using prodrugs of acyclovir is that they have improved bioavailability, which means that they can be taken orally and have better absorption and distribution in the body. This results in higher plasma concentrations of acyclovir, which allows for more effective treatment of herpes virus infections.
Idoxuridine
Idoxuridine is an antiviral drug that is used to treat herpes simplex virus infections of the eye, including keratitis and conjunctivitis. It works by inhibiting viral DNA synthesis, which prevents the virus from replicating and spreading to other cells.
Idoxuridine is a nucleoside analog, which means that it is structurally similar to the nucleosides that are used to build DNA. Once it enters the infected cell, it is phosphorylated by cellular enzymes into its active form, which is incorporated into the viral DNA chain by viral DNA polymerase.
Once incorporated, idoxuridine disrupts the normal base pairing between nucleotides, which causes mutations and errors in the viral DNA chain. This disrupts the ability of the virus to replicate and ultimately leads to the death of the infected cell and a reduction in the viral load.
Idoxuridine is typically administered as an ophthalmic solution, which is applied directly to the affected eye. While it is effective in treating herpes simplex virus infections of the eye, it is not effective in treating other types of herpes virus infections.
HIV reverse transcriptase inhibitors
HIV reverse transcriptase inhibitors are a class of antiviral drugs that target the enzyme reverse transcriptase, which is essential for the replication of the human immunodeficiency virus (HIV). These drugs work by inhibiting the ability of reverse transcriptase to convert the viral RNA genome into DNA, which is necessary for the virus to integrate into the host cell’s DNA and replicate.
There are two types of reverse transcriptase inhibitors: nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs).
NRTIs are structurally similar to the nucleosides that are used to build DNA and work by competing with the natural nucleotides for incorporation into the growing viral DNA chain. Once incorporated, they inhibit the activity of reverse transcriptase and prevent the replication of the virus. Examples of NRTIs include zidovudine (AZT), lamivudine (3TC), and tenofovir.
NNRTIs, on the other hand, bind to a specific site on reverse transcriptase and alter its structure, which inhibits its activity. They do not require phosphorylation to become active and do not compete with natural nucleotides for incorporation into the viral DNA chain. Examples of NNRTIs include efavirenz, nevirapine, and rilpivirine.
Reverse transcriptase inhibitors are often used in combination with other antiviral drugs, such as protease inhibitors and integrase inhibitors, to create highly active antiretroviral therapy (HAART) regimens. These combinations are highly effective in suppressing viral replication and preventing the progression of HIV to AIDS.
HIV Protease inhibitors
HIV protease inhibitors are a class of antiviral drugs that target the protease enzyme, which is essential for the replication of the human immunodeficiency virus (HIV). These drugs work by inhibiting the activity of the protease enzyme, which is required for the production of new viral particles.
The protease enzyme is responsible for cleaving the long chain of viral proteins into smaller, functional proteins that are needed to assemble new viral particles. Protease inhibitors block this cleavage process and prevent the production of new viral particles, thereby reducing the viral load in the body.
Some examples of HIV protease inhibitors include saquinavir, ritonavir, indinavir, nelfinavir, and darunavir. These drugs are typically taken in combination with other antiviral drugs, such as reverse transcriptase inhibitors, to create highly active antiretroviral therapy (HAART) regimens.
While HIV protease inhibitors are highly effective in suppressing viral replication, they can have side effects, including gastrointestinal problems, lipodystrophy, and metabolic disorders. In addition, the emergence of drug-resistant strains of HIV has limited the long-term effectiveness of protease inhibitors, leading to the development of new drugs and drug combinations for the treatment of HIV.
SARS COV2 Inhibitors
RNA polymerase inhibitors: These drugs target the RNA polymerase enzyme, which is essential for the replication of the SARS-CoV-2 genome. Some examples of RNA polymerase inhibitors being studied include remdesivir and molnupiravir.
Protease inhibitors: These drugs target the protease enzyme, which is essential for the processing of viral proteins that are required for the assembly of new viral particles. Some examples of protease inhibitors being studied include lopinavir and ritonavir.
Spike protein inhibitors: These drugs target the spike protein on the surface of the SARS-CoV-2 virus, which is essential for its attachment and entry into human cells. Some examples of spike protein inhibitors being studied include monoclonal antibodies, such as bamlanivimab and casirivimab/imdevimab.
Fusion inhibitors: These drugs target the fusion of the SARS-CoV-2 virus with human cells, which is essential for viral entry and infection. Some examples of fusion inhibitors being studied include umifenovir and nafamostat.
