Ensitrelvir: Oral Anti-COVID Drug 

Why in News?

The Phase 3 SCORPIO-PEP trial demonstrated that Ensitrelvir (brand name: XOCOVA) can prevent COVID-19 when given to household contacts within 72 hours of exposure to an infected individual. 

This makes SCORPIO-PEP the first and only Phase 3 study of an oral antiviral to meet the primary endpoint of preventing symptomatic COVID-19 following exposure to an infected person.  Ensitrelvir is currently under review by the US Food and Drug Administration (FDA).

Understanding how SARS-CoV-2 replicates?

• The SARS-CoV-2 virus stores much of its protein material in the form of a long protein chain called a polyprotein. This chain must be cut into smaller functional proteins before the virus can reproduce.
• Two viral enzymes perform this cutting:
  • Main Protease (Mpro): performs most of the cleavage work.
  • Papain-like Protease (PLpro): cuts specific sites not handled by Mpro.

Without these proteases, the virus cannot complete its replication cycle. Thus, these enzymes became attractive targets for antiviral drug development soon after the SARS-CoV-2 genome was published in 2020.

What is Ensitrelvir? 

• Ensitrelvir is an oral antiviral drug developed by the Japanese pharmaceutical company Shionogi for treating COVID-19 infections.
• Mechanism: It prevents the SARS-CoV-2 virus from multiplying by selectively targeting a critical viral enzyme, called the Main Protease (Mpro), which is essential for the replication of the SARS-CoV-2 virus. 
• Administering Ensitrelvir within 72 hours of symptom onset in the primary infected patient can significantly reduce transmission and symptomatic disease.

The drug has now demonstrated effectiveness not only in treating infection but also in preventing symptomatic disease after exposure. 

Why are Antiviral drugs difficult to develop? 

Developing antiviral medicines is far more challenging than producing antibiotics against bacteria.

• Viruses depend on Host Cells: Unlike bacteria, which have rigid cell walls, unique ribosomes, and metabolic pathways absent in human cells, viruses do not have independent cellular machinery. They use the host’s cellular machinery for survival and replication. Therefore, drugs targeting viruses can also unintentionally damage healthy human cells.
• Absence of Broad-Spectrum Antivirals: Most antiviral drugs are virus-specific because viruses differ significantly from one another. As a result, there is no broad-spectrum antiviral drug comparable to a broad-spectrum antibiotic. Most antiviral drugs must be designed specifically for a particular virus or, at best, for a group of closely related viruses that share similar proteins.
• Cost and timeline of drug development: On average, developing a new drug takes 8 to 12 years and costs over $2 billion. Developing antivirals individually for each new pathogen is neither fast enough nor economically scalable for pandemic preparedness. 

PDF