Neuraminidase inhibitors

A 64-year-old woman presents to the emergency department with a fever and chills for the past 24 hours. She started feeling very tired last night and soon developed alternating bouts of fevers and chills. She has not had a cough or runny nose. On review of symptoms, the patient has diffuse myalgias. She has not had any sick contacts. Past medical history is significant for mild chronic obstructive pulmonary disease. She does not require supplemental oxygen but uses a tiotropium inhaler. Temperature is 38.2°C (100.8°F), blood pressure is 105/79 mmHg, heart rate is 101/min, and respiratory rate is 10/min. Oxygen saturation is 94% on room air. On physical examination, the patient appears fatigued, and her skin is warm to the touch. A pulmonary exam is significant for rhonchi. Nasopharyngeal PCR swab is positive for influenza A. Which of the following is the most appropriate next step in management?

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Oseltamivir p. 196

Neuraminidase inhibitors are antiviral medications mainly used to treat influenza, which is the virus that causes the flu.

There are three types of influenza viruses that infect humans; type A, type B, and type C, and each one has a slightly different genome and set of proteins.

Now, neuraminidase inhibitors work by preventing the release of new viruses from infected cells, thereby limiting the duration of the illness.

Alright, first let’s focus on influenza A and influenza B.

These viruses have two types of glycoproteins on their protective envelope: H protein, or hemagglutinin; and N protein, or neuraminidase.

When the flu virus enters the body, it uses hemagglutinin to bind to sialic acid sugars on the surface of epithelial cells in the upper respiratory tract.

Once bound, the cell swallows up the virus in a process called endocytosis.

Next, the virus releases its viral RNA which moves into the cell’s nucleus.

Now, these RNAs are negative-sense, meaning they need to be transcribed by RNA polymerase into positive-sense mRNA strands.

These strands leave the nucleus and are translated into proteins by ribosomes.

These proteins are then assembled into new viruses.

Now that we have a cell that’s pretty much a virus-producing factory, it will continue to produce more and more viruses which bud off the host cell’s plasma membrane and leave the body.

However, the same hemagglutinin that allowed the virus to attach to the sialic acid sugar on the cell surface, can bind to these sugars again and prevent the viruses from leaving the host cell.

So, in order to be released, the virus uses the neuraminidase proteins to cleave the sialic acid and free itself.

So in short, hemagglutinin allows the virus to enter the cell, while neuraminidase lets the virus leave the cell.

Now, neuraminidase inhibitors, as their name implies, bind and inhibit the enzyme neuraminidase, thereby preventing the release of new viruses.

Common medications in this class include oseltamivir, which is taken perorally as a pill, and zanamivir, which is taken as a powder inhaled by mouth.

Summary

Neuraminidase inhibitors are antiviral medications used for the treatment and prophylaxis of influenza A and influenza B, which are known to cause the flu. Neuraminidase inhibitors work by blocking an enzyme called neuraminidase produced by the influenza virus. The function of neuraminidase is to help new viruses to get released from infected cells, and so, its inhibition will disrupt further infection of the host's cells. Examples of neuraminidase inhibitors include oseltamivir, and zanamivir.

Sources

"Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)

"Rang and Dale's Pharmacology" Elsevier (2019)

"Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)

"Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients" European Respiratory Journal (2015)

"Use of neuraminidase inhibitors in primary health care during pandemic and seasonal influenza between 2009 and 2013" Antiviral Therapy (2015)

"Clinical use of approved influenza antivirals: therapy and prophylaxis" Influenza and Other Respiratory Viruses (2012)

Neuraminidase inhibitors

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