Drugs against broad-spectrum of coronaviruses

The continuous emergence of severe acute respiratory type 2 coronavirus (SARS-CoV-2) variants (e.g., Omicron) and the threat of future emerging coronavirus pandemics highlight the urgent need for broad-spectrum antiviral strategies. While various therapeutics exist, a systematic integration of diverse treatment modalities remains lacking. This review introduces a comprehensive conceptual framework that compares and integrates four major therapeutic categories: small-molecule drugs (targeting viral enzymes), macromolecular drugs (including peptides and polymers), Traditional Chinese Medicine (TCM, focusing on holistic regulation and active ingredients), and carrier vector vaccines. Beyond traditional pharmacology, we further incorporate the emerging role of Artificial Intelligence (AI) and computational screening in accelerating the discovery of broad-spectrum inhibitors. The primary goal of this article is to: (1) critically analyze the distinct antiviral mechanisms, advantages, and limitations of each category; (2) explore synergistic combination therapies (e.g., combining antiviral drugs with immunomodulators or TCM) to overcome drug resistance; and (3) provide a strategic reference for developing "pan-coronavirus" therapeutics that are resilient against viral mutations.