Table 3.

Non-Eosinophilic Immunological Targets for COPD and AECOPD

Targets	Drug/Compound	Nature of drug	Mechanism	Therapy For	Developmental Stage	References
PAFr	CV-3988	_	Reduces bacterial adherence	COPD	Pre-clinical	[63]
	WEB-2086	_	Inhibits inflammatory pathways	COPD	Pre-clinical	[64]
	Simvastatin	Statin	Reduces PAFr expression and decreases bacterial load after pneumococcal infections	COPD	Approved for other indications	[65]
	Safflower yellow	Chinese herb	Affective for AECOPD treatment	AECOPD	Limited clinical evidence	[66,67]
	SR27417	_	Inhibits inflammatory pathways	COPD	Pre-clinical	[47]
ICAM-1 antagonist (binds to domain 1 of human ICAM-1)	14C11	Mouse anti-human ICAM-1 antibody	Reduces inflammation, pro-inflammatory cytokine production, and viral loads	COPD	Pre-clinical	[68,69]
SA	_	Small peptides	Inhibits viral entry in cell	COPD	Pre-clinical	[70]
SA + EGFR	_	Monoclonal antibodies	Inhibits viral entry in cell + Downstream the signalling of EGFR	COPD	Pre-clinical	[71–74]
SA	_	Dendritic polymers	Inhibits viral entry in cell	COPD	Pre-clinical	[75]
TLR	Ulinastatin	Protease inhibitor	Suppress TLR signaling and inflammatory response	COPD	In vivo trials (Phase II)	[76]
	Sulforaphane	_	Reduces inflammatory response	COPD	Pre-clinical trials	[77,78]
	Bufei Yishen	Chinese herb	Inhibits TLR and reduces inflammatory response	COPD	In-vivo trials	[79]
TLR + PKC	Resveratrol	Polyphenol	Suppresses TLR response and reduces inflammatory response + Disrupt PKC-related pathways	COPD	Pre-clinical	[80,81]
PKC	Defensins	Antimicrobial peptides	Inhibits PKC	COPD	Pre-clinical	[82–84]
PI3K	Nemiralisib	PI3Kδ inhibitor	Reduces inflammation and viral susceptibility	_	Phase II	[85]
EGFR	Fucoidan	Sulfated polysaccharide from algae	Enhances immune responses and prevent EGFR-mediated viral entry	_	Phase II	[86–88]
Macrophages	Roflumilast	PDE-4 inhibitor	Favors a more reparative M2 macrophage phenotype	_	Phase III	[89]
	_	Macrolides	Improve phagocytic function in alveolar macrophages	AECOPD	_	[90]
	_	Statins	Improve phagocytic function in alveolar macrophages	_	Pre-clinical	[91]
PDE3 and PDE4	Ensifentrine	_	Dual inhibition increases cAMP/cGMP levels, leading to bronchodilation and anti-inflammatory effects.	COPD & AECOPD	Approved (2024)	[92]