The coronavirus disease 2019 (COVID‐19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that the rapidly evolving coronavirus subvariants risk rendering vaccines and antibodies ineffective due to their potential to evade existing immunity, with enhanced transmission activity and higher reinfection rates that could lead to new outbreaks across the globe. The goal of viral management is to disrupt the viral life cycle as well as to relieve severe symptoms such as lung damage, cytokine storm, and organ failure. In the fight against viruses, the combination of viral genome sequencing, elucidation of the structure of viral proteins, and identifying proteins that are highly conserved across multiple coronaviruses has revealed many potential molecular targets. In addition, the time‐ and cost‐effective repurposing of preexisting antiviral drugs or approved/clinical drugs for these targets offers considerable clinical advantages for COVID‐19 patients. This review provides a comprehensive overview of various identified pathogenic targets and pathways as well as corresponding repurposed approved/clinical drugs and their potential against COVID‐19. These findings provide new insight into the discovery of novel therapeutic strategies that could be applied to the control of disease symptoms emanating from evolving SARS‐CoV‐2 variants.

Chimeric antigen receptor (CAR)-T cell therapy has transformed treatment of relapsed/refractory DLBCL, yet resistance driven by regulatory T cells (Tregs) limits its efficacy. Here we identify Timosaponin AIII (TAIII), a clinical-stage natural product, as an effective modulator of CAR-T function that depletes CAR-Tregs while enhancing effector activity. Mechanistically, TAIII acts as an allosteric A2AR inhibitor by competing with cholesterol, suppressing CREB-dependent FoxP3 transcription and disrupting the A2AR-Treg axis. Ablation of A2AR or Tregs in vitro and in vivo abolishes TAIII activity, confirming specificity. Furthermore, TAIII reduces intratumoral Tregs, increases CD8⁺ T cells infiltration, and potentiates PD-1 blockade in solid tumor models. Importantly, TAIII promotes central memory T-cell formation and enhances CAR-T cytotoxic cytokine secretion. Combining or pretreating CAR-T cells with TAIII markedly improves antitumor efficacy and prevents late relapse across preclinical models. These findings establish TAIII as a combinatorial strategy to deplete CAR-Tregs, enhance CAR-T activity, and extend therapeutic durability.