Vaccines and Antiviral Drugs for Treatment


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Part a shows the structure of the influenza virus, which is icosahedral with a viral envelope. Neuraminidase and hemagglutinin are embedded in the envelope. Part b shows that Tamiflu prevents the step in influenza infection in which virions leave the cell.
Action of an antiviral drug. (a) Tamiflu inhibits a viral enzyme called neuraminidase (NA) found in the influenza viral envelope. (b) Neuraminidase cleaves the connection between viral hemagglutinin (HA), also found in the viral envelope, and glycoproteins on the host cell surface. Inhibition of neuraminidase prevents the virus from detaching from the host cell, thereby blocking further infection. (credit a: modification of work by M. Eickmann)

OpenStax Biology 2e

In some cases, vaccines can be used to treat an active viral infection. The concept behind this is that by giving the vaccine, immunity is boosted without adding more disease-causing virus. In the case of rabies, a fatal neurological disease transmitted via the saliva of rabies virus-infected animals, the progression of the disease from the time of the animal bite to the time it enters the central nervous system may be two weeks or longer. This is enough time to vaccinate individuals who suspect that they have been bitten by a rabid animal, and their boosted immune response is sufficient to prevent the virus from entering nervous tissue. Thus, the potentially fatal neurological consequences of the disease are averted, and the individual only has to recover from the infected bite. This approach is also being used for the treatment of Ebola, one of the fastest and most deadly viruses on Earth. Transmitted by bats and great apes, this disease can cause death in 70 to 90 percent of infected humans within two weeks. Using newly developed vaccines that boost the immune response in this way, there is hope that affected individuals will be better able to control the virus, potentially saving a greater percentage of infected persons from a rapid and very painful death.

Another way of treating viral infections is the use of antiviral drugs. Because viruses use the resources of the host cell for replication and the production of new virus proteins, it is difficult to block their activities without damaging the host. However, we do have some effective antiviral drugs, such as those used to treat HIV and influenza. Some antiviral drugs are specific for a particular virus and others have been used to control and reduce symptoms for a wide variety of viral diseases. For most viruses, these drugs can inhibit the virus by blocking the actions of one or more of its proteins. It is important to note that the targeted proteins be encoded by viral genes and that these molecules are not present in a healthy host cell. In this way, viral growth is inhibited without damaging the host.

Antivirals have been developed to treat genital herpes (herpes simplex II) and influenza. For genital herpes, drugs such as acyclovir can reduce the number and duration of episodes of active viral disease, during which patients develop viral lesions in their skin cells. As the virus remains latent in nervous tissue of the body for life, this drug is not curative but can make the symptoms of the disease more manageable. For influenza, drugs like Tamiflu (oseltamivir) can reduce the duration of “flu” symptoms by one or two days, but the drug does not prevent symptoms entirely. Tamiflu works by inhibiting an enzyme (viral neuraminidase) that allows new virions to leave their infected cells. Thus, Tamiflu inhibits the spread of virus from infected to uninfected cells. Other antiviral drugs, such as Ribavirin, have been used to treat a variety of viral infections, although its mechanism of action against certain viruses remains unclear.

By far, the most successful use of antivirals has been in the treatment of the retrovirus HIV, which causes a disease that, if untreated, is usually fatal within 10 to 12 years after infection. Anti-HIV drugs have been able to control viral replication to the point that individuals receiving these drugs survive for a significantly longer time than the untreated.

Anti-HIV drugs inhibit viral replication at many different phases of the HIV replicative cycle. Drugs have been developed that inhibit the fusion of the HIV viral envelope with the plasma membrane of the host cell (fusion inhibitors), the conversion of its RNA genome into double-stranded DNA (reverse transcriptase inhibitors, like AZT), the integration of the viral DNA into the host genome (integrase inhibitors), and the processing of viral proteins (protease inhibitors).

The illustration shows the steps in the H I V life cycle. In step 1, g p 120 glycoproteins in the viral envelope attach to a C D 4 receptor on the host cell membrane. The glycoproteins then attached to a co-receptor, C C R 5 or C X C R 4, and the viral envelope fuses with the cell membrane. H I V, R N A, reverse transcriptase, and other viral proteins are released into the host cell. Viral D N A is formed from R N A by reverse transcriptase. Viral D N A is then transported across the nuclear membrane, where it integrates into the host D N A. New viral R N A is made; it is used as genomic R N A and to make viral proteins. New viral R N A and proteins move to the cell surface and a new, immature H I V forms. The virus matures when a protease releases individual H I V proteins.
Life cycle of HIV. HIV, an enveloped, icosahedral virus, attaches to the CD4 receptor of an immune cell and fuses with the cell membrane. Viral contents are released into the cell, where viral enzymes convert the single-stranded RNA genome into DNA and incorporate it into the host genome. (credit: NIAID, NIH)

Unfortunately, when any of these drugs are used individually, the high mutation rate of the virus allows it to easily and rapidly develop resistance to the drug, limiting the drug’s effectiveness. The breakthrough in the treatment of HIV was the development of HAART, highly active anti-retroviral therapy, which involves a mixture of different drugs, sometimes called a drug “cocktail.” By attacking the virus at different stages of its replicative cycle, it is much more difficult for the virus to develop resistance to multiple drugs at the same time. Still, even with the use of combination HAART therapy, there is concern that, over time, the virus will develop resistance to this therapy. Thus, new anti-HIV drugs are constantly being developed with the hope of continuing the battle against this highly fatal virus.

Source:

Clark, M., Douglas, M., Choi, J. Biology 2e. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/biology-2e