Antiviral drug
[7] The emergence of antivirals is the product of a greatly expanded knowledge of the genetic and molecular function of organisms, allowing biomedical researchers to understand the structure and function of viruses, major advances in the techniques for finding new drugs, and the pressure placed on the medical profession to deal with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS).
[8] The first experimental antivirals were developed in the 1960s, mostly to deal with herpes viruses, and were found using traditional trial-and-error drug discovery methods.
For example, a researcher might target a critical enzyme synthesized by the virus, but not by the patient, that is common across strains, and see what can be done to interfere with its operation.
The cells are then cultured for mass production of the protein, which can then be exposed to various treatment candidates and evaluated with "rapid screening" technologies.
Researchers working on such "rational drug design" strategies for developing antivirals have tried to attack viruses at every stage of their life cycles.
[18] Pleconaril works against rhinoviruses, which cause the common cold, by blocking a pocket on the surface of the virus that controls the uncoating process.
Vaccines that combine dozens of varieties of rhinovirus at once are effective in stimulating antiviral antibodies in mice and monkeys, researchers reported in Nature Communications in 2016.
Another target being considered for HIV antivirals include RNase H—which is a component of reverse transcriptase that splits the synthesized DNA from the original viral RNA.
Once a virus genome becomes operational in a host cell, it then generates messenger RNA (mRNA) molecules that direct the synthesis of viral proteins.
Genomics has not only helped find targets for many antivirals, it has provided the basis for an entirely new type of drug, based on "antisense" molecules.
In contrast, uninfected mammalian cells generally produce dsRNA helices of fewer than 24 base pairs during transcription.
DRACO (double-stranded RNA activated caspase oligomerizer) is a group of experimental antiviral drugs initially developed at the Massachusetts Institute of Technology.
The procaspases transactivate via cleavage, activate additional caspases in the cascade, and cleave a variety of cellular proteins, thereby killing the cell.
Two drugs named zanamivir (Relenza) and oseltamivir (Tamiflu) that have been recently introduced to treat influenza prevent the release of viral particles by blocking a molecule named neuraminidase that is found on the surface of flu viruses, and also seems to be constant across a wide range of flu strains.
A more specific approach is to synthesize antibodies, protein molecules that can bind to a pathogen and mark it for attack by other elements of the immune system.
A monoclonal drug is now being sold to help fight respiratory syncytial virus in babies,[39] and antibodies purified from infected individuals are also used as a treatment for hepatitis B.
[41] The three FDA-approved neuraminidase antiviral flu drugs available in the United States, recommended by the CDC, include: oseltamivir (Tamiflu), zanamivir (Relenza), and peramivir (Rapivab).
[41] Influenza antiviral resistance often results from changes occurring in neuraminidase and hemagglutinin proteins on the viral surface.
Furthermore, a study published in 2009 in Nature Biotechnology emphasized the urgent need for augmentation of oseltamivir stockpiles with additional antiviral drugs including zanamivir.
This finding was based on a performance evaluation of these drugs supposing the 2009 H1N1 'Swine Flu' neuraminidase (NA) were to acquire the oseltamivir-resistance (His274Tyr) mutation, which is currently widespread in seasonal H1N1 strains.
[47] RNA viruses also have small genome sizes that are typically less than 30 kb, which allow them to sustain a high frequency of mutations.
Billions of viruses are produced every day during the course of an infection, with each replication giving another chance for mutations that encode for resistance to occur.
[citation needed] National and international surveillance is performed by the CDC to determine effectiveness of the current FDA-approved antiviral flu drugs.
WHO further recommends in-depth epidemiological investigations to control potential transmission of the resistant virus and prevent future progression.
The most commonly used method for treating resistant viruses is combination therapy, which uses multiple antivirals in one treatment regimen.
In this context it serves to distinguish these drugs from those with an indirect mechanism of action such as immune modulators like interferon alfa.
Furthermore, in local health departments (LHDs) with access to antivirals, guidelines may be unclear, causing delays in treatment.
Overall, national guidelines, regarding infection control and management, standardize care and improve healthcare worker and patient safety.
Also managed by the CDC, the Strategic National Stockpile (SNS) consists of bulk quantities of medicines and supplies for use during such emergencies.
During the H1N1 pandemic in 2009–2010, guidelines for SNS use by local health departments was unclear, revealing gaps in antiviral planning.
