Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.
【저자키워드】 COVID-19, Drug repurposing, SARS-CoV-2, Cytokine storm, approved drugs, lysosomotropism, metabolites, viral host cell entry, pulmonary tissue accumulation, eligibility criteria, 【초록키워드】 Treatment, coronavirus disease, coronavirus, pandemic, Chloroquine, Stress, IL-6, SARS-COV-2 infection, drugs, cytokine, drug, severe acute respiratory syndrome Coronavirus, viral entry, viral infections, Cytokine release syndrome, Prophylaxis, Viral, Patient, Small molecules, stress response, targets, systemic inflammation, respiratory, characteristic, disease, metabolite, compounds, Bacterial, cathepsin, CRS, lysosome, Hypothesis, Inflammatory, Lysosomes, host cells, cathepsin L, second messengers, biological characteristic, approved drug, endothelial, acute respiratory syndrome, acute respiratory syndrome coronavirus, tissue, acute respiratory syndrome coronavirus 2, profile, enrichment, transition, candidate, heterogeneous group, hydroxy, pulmonary tissue, pharmacological, lysosomal enzymes, Affect, Effects, intrinsic, receiving, condition, triggered, cathepsin L-dependent, lysosomal enzyme, OTC, 【제목키워드】 Multiple, targeting, Progress,