Antivirals

Introduction to Antivirals

Antivirals are a class of medications designed to treat viral infections (including those responsible for diseases such as influenza, HIV/AIDS, hepatitis, and herpes.) by inhibiting the development and replication of viruses within the host. For examples, they can block viral entry into host cells, inhibit viral enzymes essential for replication, or prevent the assembly of new viral particles. The development of antiviral therapies has significantly improved patient outcomes, reduced the severity of infections and the duration of symptoms, while also contributing to preventive strategies, especially in the case of vaccines. However, the emergence of antiviral resistance remains a significant challenge in the management of viral diseases.

Classification of Antivirals

Antivirals can be manufactured from several different types of components, broadly categorized into small molecule drugs and biologic agents, depending on their size and structure.

How Do Antivirals Work?

Viruses must complete a series of tightly regulated steps to reproduce inside host cells. Antiviral drugs work by blocking one or more of the seven stages of the viral life cycle ^[1], which include:

• Attachment Inhibition: This is the initial step where the virus binds to specific receptors on the host cell surface. Some antivirals prevent this attachment by binding either to the virus's surface proteins or to the host cell receptors, effectively blocking viral entry.
• Penetration Inhibition: After attachment, viruses penetrate the host cell membrane via fusion or endocytosis. Fusion inhibitors (such as Enfuvirtide) block this process, especially in enveloped viruses like HIV or RSV.
• Uncoating Inhibition: Once inside the cell, the virus sheds its protein coat to release its genetic material. Uncoating inhibitors (such as Amantadine) interfere with this process, preventing the release of viral nucleic acids.
• Replication Inhibition: During this stage, the viral genome is copied. This is one of the most common targets for antiviral drugs. Agents like nucleoside/nucleotide analogues mimic the natural building blocks of viral DNA or RNA and cause premature chain termination.
• Assembly Inhibition: Viral components such as proteins and nucleic acids must be assembled into new viral particles. Although not as commonly targeted, some drugs inhibit this process, interfering with proper virion formation.
• Maturation Inhibition: Even after assembly, many viruses require post-processing (e.g., cleavage of polyproteins) to become infectious. Ritonavir and other HIV protease inhibitors can block this step, resulting in non-functional viruses.
• Release Inhibition: In the final stage, new virions must exit the host cell to infect others. Neuraminidase inhibitors prevent the release of influenza viruses by blocking a viral enzyme necessary for detachment from the host cell membrane. Example includes oseltamivir.

Fig. 1. Antivirals target seven stages of the viral replication cycle to inhibit their ability to proliferate.

What Do Antivirals Treat?

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