Influenza virus being attacked by beams of antiviral drugs.

Flu Fight: Can Combining Antivirals Be the Ultimate Weapon?

Nico Varela in Health & Wellness November 2025 • 4 min read.

"New research explores how different antiviral drug combinations could offer a more effective strategy against influenza."

The flu, more formally known as influenza, is a seasonal illness bringing a constellation of symptoms like runny noses, coughs, and fevers. For most, recovery is swift, but influenza can be dangerous, especially for the very young and the elderly. While vaccines offer a preventative measure, their strain-specificity and annual updates can sometimes leave people vulnerable. This is where antiviral medications step in as a crucial defense.

However, the effectiveness of antivirals is challenged by influenza's rapid mutation rate, leading to antiviral resistance. Currently, only two classes of antiviral drugs are widely approved, limiting treatment options. The development of new antivirals targeting different stages of the viral replication cycle offers a glimmer of hope, especially when considering combination therapies.

Combination therapy involves using two or more antivirals simultaneously, potentially reducing drug resistance and treatment costs. To explore this, researchers are investigating how different antiviral mechanisms of action pair in combination to maximize therapeutic benefits. A mathematical model of influenza is being used to simulate combination treatments and measure key outcomes such as peak viral load, infection duration, and synergistic effects.

Why Isn't One Antiviral Enough?

Influenza virus being attacked by beams of antiviral drugs.

Influenza's ability to quickly develop resistance to single antivirals makes combination therapy an appealing strategy. Developing resistance to two drugs simultaneously takes considerably longer. By using multiple drugs, the likelihood that the virus can fully evade treatment is reduced, ensuring that most of the virus produced remains susceptible to at least one of the drugs. This approach can effectively suppress the infection.

Numerous experimental studies have explored various combinations of influenza antivirals, with some even testing triple combinations. Traditionally, these studies have focused on combining drugs from the two main classes: neuraminidase inhibitors (NAIs) and adamantanes. However, the emergence of new antivirals with different mechanisms of action opens new possibilities for combination therapies.

Neuraminidase Inhibitors (NAIs): Block viral release, preventing the virus from spreading to new cells.
Adamantanes: Block viral replication, preventing the virus from multiplying within cells.
Polymerase Complex Inhibitors: Interfere with the virus's ability to replicate its genetic material.

Exploring how antiviral mechanisms of action affect the effectiveness of combination therapy is a growing area of interest. In vitro experiments are often conducted to assess the synergy or antagony of drug combinations. Synergy occurs when the combined effect is greater than the sum of individual effects, while antagony indicates a smaller effect. Mathematical models are now being leveraged to efficiently simulate numerous dose combinations and identify optimal treatment strategies.

What Does This Mean for Future Flu Treatments?

This research underscores the importance of understanding how different antiviral mechanisms interact in combination therapies. By identifying which combinations are most effective, clinicians and drug developers can design more effective treatment strategies. As new antivirals continue to emerge, considering their mechanisms of action and potential for synergy will be crucial in combating influenza and reducing the risk of antiviral resistance.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3389/fphar.2018.01207, Alternate LINK

Title: Investigating Different Mechanisms Of Action In Combination Therapy For Influenza

Subject: Pharmacology (medical)

Journal: Frontiers in Pharmacology

Publisher: Frontiers Media SA

Authors: Kelli Melville, Thalia Rodriguez, Hana M. Dobrovolny

Published: 2018-10-23

Everything You Need To Know

Why is combination therapy being explored as a strategy to combat influenza?

Influenza's rapid mutation rate allows it to develop resistance to single antivirals quickly. Using multiple drugs simultaneously, known as combination therapy, makes it more difficult for the virus to evade treatment because developing resistance to two drugs is significantly harder than developing resistance to one. This ensures that the majority of the virus remains susceptible to at least one of the drugs, effectively suppressing the infection.

What does combination therapy entail in the context of influenza treatment, and what does research involve?

Combination therapy for influenza involves using two or more antivirals simultaneously. The primary goal is to reduce the likelihood of drug resistance and potentially lower treatment costs. Experimental studies have explored combinations, traditionally focusing on neuraminidase inhibitors (NAIs) and adamantanes. Newer antivirals with different mechanisms of action are expanding possibilities. Mathematical models help simulate treatments and identify optimal strategies.

What are the main classes of antiviral drugs currently being explored for influenza, and how do their mechanisms of action differ?

The three classes of influenza antivirals discussed are neuraminidase inhibitors (NAIs), adamantanes, and polymerase complex inhibitors. Neuraminidase inhibitors (NAIs) work by blocking the release of the virus from infected cells, preventing it from spreading to new cells. Adamantanes block viral replication, preventing the virus from multiplying within cells. Polymerase complex inhibitors interfere with the virus's ability to replicate its genetic material. These different mechanisms offer various targets within the viral lifecycle.

In the context of antiviral combinations, what do 'synergy' and 'antagony' mean, and why are they important?

Synergy in antiviral combination therapy refers to when the combined effect of two or more drugs is greater than the sum of their individual effects. This is highly desirable as it maximizes the therapeutic benefit. Antagony, on the other hand, occurs when the combined effect is smaller than the sum of individual effects, indicating that the drugs are interfering with each other. Understanding synergy and antagony is crucial for designing effective combination therapies, and in vitro experiments and mathematical models are used to assess these interactions.

What are the potential long-term implications for influenza treatment strategies given the research into antiviral drug combinations?

Understanding how different antiviral mechanisms interact in combination therapies is vital for designing more effective treatment strategies. As new antivirals emerge, considering their mechanisms of action and potential for synergy will be crucial in combating influenza and reducing the risk of antiviral resistance. This research can guide clinicians and drug developers in creating treatments that are more robust against evolving influenza strains. This is particularly important because influenza's high mutation rate and the limitations of current vaccines can leave individuals susceptible to infection.