Two antiviral drugs for influenza A are available on the market: M2 proton channel blockers and neuraminidase inhibitors. M2 proton channel inhibitors effectively block the M2 ion channel. Hence, they inhibit the influx of protons from the acidified endosome into the infected virion during virus entry; this endosomal acidification facilitates the disassembly of the viral structure, allows the RNA to enter the host nucleus, and subsequently initiates a round of viral replication. These agents have no activity against influenza B, almost all A/H3N2 viruses and many human isolates of avian A/H5N1 viruses. Neuraminidase inhibitors interfere with the enzymatic activity of influenza A and B neuraminidase, which is one of three transmembrane proteins coded by the influenza genome. This enzymatic activity is necessary for the release and dispersal of progeny viral particles from the infected cells. Neuraminidase inhibitors are active against influenza A and B viruses, including the avian H5N1 strain.

Serine-to-asparagine mutation at amino acid position 31 on the M2 gene of S-OIV demonstrates its resistance to ion channel blockers: amantadine and rimantadine.

Instead, this virus responds to the neuraminidase inhibitors: oseltamivir and zanamivir. Although both drugs are well tolerated, oseltamivir is the drug of choice because of its convenient administration route, which is oral.

Many factors affect treatment decision: the disease prevalence in the region, a history of contact, characteristics of the illness, presence of established complications, comorbidities and risk factors, onset of illness, availability of antiviral agents, and the healthcare policies. In seasonal influenza patients, early antiviral therapy (within 36–48 h of symptom onset) mitigates the length of symptoms, antibiotic use, morbidity, and recovery time.

Oseltamivir treatment correlates with survival of hospitalised pneumonia patients caused by human influenza A/ H3N2, A/H1N1 or Swine flu or B viruses.

The updated WHO guidelines suggest antiviral therapy be started within 72 h from the onset of the symptoms in patients with (1) shortness of breath, hypoxia, and fast or laboured  respiration in children which indicates cardiopulmonary; (2)  ahy central nervous system symptoms like drowsiness, unconsciousness, seizures and altered mental status; (3) there is symptoms of sustained viral replication or bacterial infection is there (4) there is severe dehydration which is expressed as decreased activity,dizziness, lethargy and less urine output is there.

However, mass use of antiviral drugs could potentially lead to selection pressure for antiviral drug resistance. Seasonal H1N1 influenza viruses or Swine flu resistant to oseltamivir have strikingly

increased over the past few years. Notably, antiviral-resistant strains may spread rapidly, affecting the pandemic outcomes. As of 22 October 2009, the WHO announced  confirmed cases with oseltamivir-resistant S-OIV variants, regardless of immunocompromised status and history of oseltamivir use. Zanamivir is recommended in patients infected with oseltamivir-resistant influenza viruses.28 Primary influenza pneumonitis is best treated with oseltamivir. Secondary bacterial pneumonia requires appropriate antibiotics; common causative agents include group A streptococcus, Staphylococcus aureus and Streptococcus pneumoniae. Research on other antiviral drugs such as peramivir, CS-8958, T-705, and monoclonal antibodies to HA proteins, is under way. On 24 October 2009, the US President Barack Obama has declared H1N1 influenza or Swine flu to be a national emergency. Meanwhile, the US Food and Drug Administration (FDA) has authorised emergency use of peramivir, the only intravenous neuraminidase inhibitor, in hospitalised patients with antiviral-resistant SOIV strains, even though this drug has not been approved for seasonal vaccine, over half of them may not be willing to be immunised. Many issues on pandemic vaccines remains unclear, including appropriate doses, optimal antigen content in vaccine, duration of immune response, a risk of Guillain- Barré syndrome, and long-term safety data.

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