Influenza remains a major public health challenge, with seasonal outbreaks and pandemic threats posing a risk to global health. The treatment and prevention of influenza relies heavily on antiviral drugs that target specific viral proteins involved in replication and transmission. Understanding the mechanism of action, classification, and clinical use of antiviral drugs is critical to optimizing influenza treatment strategies.
Alfa Chemistry offers active pharmaceutical ingredients for antiviral drugs used in the treatment of influenza:
What is an influenza virus?
Influenza viruses belong to the negative-stranded ribonucleic acid (RNA) virus category and feature a segmented genome that produces glycoproteins hemagglutinin (HA), neuraminidase (NA), and matrix 2 protein (M2). The virus gains entry to cells through HA binding to cell receptors, and NA aids reproduction processes, which are key factors in disease development.
Influenza viruses are categorized into four types: A, B, C, and D. Influenza B viruses infect humans and seals, while influenza C viruses infect pigs, dogs, and humans. Influenza A viruses infect humans, birds, pigs, horses, and other mammals. Eighty percent of influenza pandemics originate from influenza A viruses, despite most influenza infections being caused by both influenza A and B viruses.
Fig.1 The structure of influenza virus[1].
How do antiviral drugs fight influenza?
Influenza viruses (both types A and B) produce multiple essential proteins required for their survival. Antiviral drugs are pharmacologic agents designed to inhibit viral replication and reduce the severity of illness. They work by blocking viral enzymes and proteins. The medications achieve the best results when administered in the first 48 hours after symptoms start, which reduces symptom duration and prevents serious complications for those at high risk.
Fig.2 Antiviral medicines that work against influenza viruses[2].
There are three classes of antiviral drugs currently used to treat or prevent influenza infection: NA inhibitors, M2 ion channel blockers, and polymerase inhibitors.
Neuraminidase inhibitors: the most widely used antiviral drugs
NA inhibitors target the NA enzyme because this surface glycoprotein of influenza A and B viruses helps viruses move through the respiratory tract and facilitates the release of new viruses from host cells. NA inhibitors work by stopping viral spread throughout the respiratory tract through their inhibitory action.
Approved NA inhibitors[3]:
| Drug | Target Action | Virus Type | Administration Route | Approval Agency | Approval Year |
| Zanamivir | Blocks viral NA activity | A & B | Nasal or Oral | FDA | 1993 |
| Oseltamivir | Blocks viral NA activity | A & B | Oral | FDA | 1998 |
| Peramivir | Blocks viral NA activity | A & B | Intramuscular, Intravenous | FDA | 2000 |
| Laninamivir | Blocks viral NA activity | A & B | Nasal | Japan | 2010 |
NA inhibitors remain the first-line treatment for influenza and are effective against both influenza A and B strains.
Alfa Chemistry provides high quality API intermediates for the development of antiviral drugs for influenza treatment. As advances in influenza treatment continue, we remain committed to supporting drug innovation in the fight against viral diseases.
M2 Ion Channel Blockers: limited use due to drug resistance
M2 is a membrane protein that enables replication of the influenza A virus M2 ion channel inhibitors, including amantadine (AMT) and amantadine, have historically been used against influenza A viruses by blocking the M2 proton channel, which is necessary for viral shedding. Influenza B viruses are not sensitive to these M2 inhibitors, despite the fact that they have M2 proteins similar to the M2 proteins of the influenza B (BM2) proteins found in influenza A. The M2 inhibitors have been shown to be resistant to these inhibitors.
Approved M2 ion channel blockers[3]:
| Drug | Target Action | Virus Type | Administration Route | Approval Agency | Approval Year |
| Amanadine | Blocks the viral uncoating and entry into the host cell | A | Oral | No longer | 1963 |
| Rimantadine | Blocks the viral uncoating and entry into the host cell | A | Oral | No longer | 1969 |
However, widespread resistance has rendered these drugs largely ineffective, leading to their exclusion from current therapeutic recommendations.
Polymerase inhibitors: targeting viral RNA synthesis
The replication of influenza A, B, C, and D viruses depends on RNA polymerase, which drives viral protein synthesis along with transcription and viral genome replication processes. The action of polymerase inhibitors involves disrupting viral RNA polymerase to interfere with transcription and genome replication.
| Drug | Class | Target Action | Virus Type | Administration Route | Approval Agency | Approval Year |
| Favipiravir | RNA polymerase inhibitor | Inhibits viral RNA-dependent RNA polymerase substrate | A & B | Oral | Japan, China | 2002 |
| Baloxavir marboxil | Polymerase acidic Endonuclease inhibitor | Inhibits the activity of cap-dependent endonuclease | A & B | Oral | FDA | 2018 |
The drug baloxavir maboxetil functions as an oral single-dose treatment approved for patients who are 5 years of age or older. Baloxavir proves effective yet remains unsuitable for pregnant or breastfeeding patients and hospitalized patients because of insufficient data.
Fig.3 Advantages of combination therapy over monotherapy. Combination therapy includes two or more drugs or immunomodulators with the same or different therapeutic targets. Antiviral combinations with different therapeutic activities can promote synergistic effects and reduce drug toxicity and resistance rates[3].
How effective are antiviral drugs in the treatment of influenza?
According to research studies early administration of antiviral therapy shortens symptom duration by approximately one day. Antivirals help decrease the chances of complications from influenza as well as hospital stays and deaths among high-risk populations such as:
- Pregnant women
- People with chronic lung disease as well as diabetes and cardiovascular disease
- Immunocompromised patients
- Older adults
How do antivirals differ from COVID-19 treatment?
The viruses responsible for influenza and COVID-19 differ despite both being respiratory viral infections because influenza is caused by the influenza virus while COVID-19 stems from SARS-CoV-2. The COVID-19 antivirals nimalivec/ritonavir (Paxlovid), monupivir, and raltegravir do not have approval for influenza treatment applications. The antiviral drugs oseltamivir and zanamivir that target influenza viruses show no effectiveness against COVID-19.
| Catalog | Product Name | |
| ACM2628280408 | PF-07321332 (Nirmatrelvir) | Inquiry |
| ACM155213675 | Ritonavir | Inquiry |
| ACM1809249373 | Remdesivir | Inquiry |
| ACM518048050 | Raltegravir | Inquiry |
Fig.4 An illustrative picture showing the drugs approved in COVID-19 therapy and their related targets[4].
Future Directions in Influenza Antiviral Drug Development
The development of antiviral resistance to NA inhibitors underscores the urgent requirement for novel treatments. Scientists are investigating advanced inhibitors and combination treatment approaches to enhance drug performance and reduce resistance problems. Scientists are currently examining how host-targeted therapies operate because they modulate the immune response instead of directly attacking viral components.
Frequently Asked Questions (FAQ)
- What are the best antiviral drugs for influenza?
The choice of antiviral medication depends on patient-specific factors. Oseltamivir is widely used because of its oral availability, while Paramivir is indicated for hospitalized patients who require intravenous administration.
- Can flu antivirals prevent infection?
Yes, oseltamivir and zanamivir can be used to prevent influenza in individuals exposed to the virus.
- Are antivirals effective if taken later?
Antiviral medications work best within 48 hours of the onset of symptoms, but later doses may still be beneficial for those at risk.
- Are there any side effects of antiviral drugs?
Common side effects include nausea, headache, and vomiting. Zanamivir may trigger bronchospasm in people with asthma or COPD.
- Is baloxavir better than oseltamivir?
Baloxavir requires only one dose and is very convenient, but oseltamivir is still more widely used due to more extensive clinical data and safety in different populations.
- Where can I buy anti-influenza virus medications?
Anti-influenza virus medications are prescription drugs and must be obtained through a healthcare provider.
References
- Langer D., et al. Potential of glycyrrhizic and glycyrrhetinic acids against influenza type A and B viruses: A perspective to develop new anti-influenza compounds and drug delivery systems. European Journal of Medicinal Chemistry (2023).
- Poelvoorde L. V., et al. Next-Generation Sequencing: An Eye-Opener for the Surveillance of Antiviral Resistance in Influenza. Trends in Biotechnology (2019).
- Batool S., et al. Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy. Microorganisms (2023).
- Esposito R., et al. Overview of Antiviral Drug Therapy for COVID-19: Where Do We Stand?. Biomedicines (2022).
