Highlights on molecular targets in the management of COVID-19: Possible role of pharmacogenomics

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Coronavirus disease 2019 (COVID-19) cases and deaths decreased by late 2022, but new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerged.
• Critically ill COVID-19 patients exhibit elevated proinflammatory cytokines, particularly interleukin-6 (IL-6).
• COVID-19 mortality is often linked to a 'cytokine storm' driven by excessive inflammatory cytokines.

Purpose of the Study:

• To review the therapeutic potential of proteasome inhibitors, protease inhibitors, and nuclear factor kappa B (NF-κB) inhibitors.
• To highlight alternative treatment strategies beyond IL-6 inhibitors for managing COVID-19 cytokine storms.

Main Methods:

• Narrative review of existing literature.
• Analysis of therapeutic targets including proteasome, protease, and NF-κB pathways.
• Evaluation of drug classes for potential COVID-19 treatment.

Main Results:

• Current recommendations include low-dose dexamethasone and IL-6 inhibitors to manage cytokine storms.
• Emerging research suggests proteasome inhibitors, protease inhibitors, and NF-κB inhibitors as alternative therapeutic avenues.
• These agents may modulate the inflammatory response implicated in COVID-19 severity.

Conclusions:

• While IL-6 inhibitors are established, other targeted therapies warrant further investigation.
• Proteasome, protease, and NF-κB inhibitors represent promising options for severe COVID-19 management.
• Exploring diverse therapeutic strategies is crucial for combating evolving SARS-CoV-2 variants and associated complications.