COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks

Int J Mol Sci. 2020 Jul 13;21(14):4953. doi: 10.3390/ijms21144953.


In line with SARS and MERS, the SARS-CoV-2/COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide. SARS-CoV-2 infection/COVID-19 provides numerous therapeutic targets, each of them promising, but not leading to the success of therapy to date. Neither an antiviral nor an immunomodulatory therapy in patients with SARS-CoV-2 infection/COVID-19 or pre-exposure prophylaxis against SARS-CoV-2 has proved to be effective. In this review, we try to close the gap and point out the likely relationships among lysosomotropism, increasing lysosomal pH, SARS-CoV-2 infection, and disease process, and we deduce an approach for the treatment and prophylaxis of COVID-19, and cytokine release syndrome (CRS)/cytokine storm triggered by bacteria or viruses. Lysosomotropic compounds affect prominent inflammatory messengers (e.g., IL-1B, CCL4, CCL20, and IL-6), cathepsin-L-dependent viral entry of host cells, and products of lysosomal enzymes that promote endothelial stress response in systemic inflammation. As supported by recent clinical data, patients who have already taken lysosomotropic drugs for other pre-existing conditions likely benefit from this treatment in the COVID-19 pandemic. The early administration of a combination of antivirals such as remdesivir and lysosomotropic drugs, such as the antibiotics teicoplanin or dalbavancin, seems to be able to prevent SARS-CoV-2 infection and transition to COVID-19.

Keywords: COVID-19; SARS-CoV-2; approved active compounds; cathepsin L; cytokine release syndrome; cytokine storm; lysosome; lysosomotropic compounds; lysosomotropism; viral host cell entry.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / physiology
  • COVID-19
  • Coronavirus 3C Proteases
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / pathology*
  • Coronavirus Infections / virology
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / pathology
  • Humans
  • Lysosomes / metabolism*
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / pathology*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / metabolism
  • Virus Internalization / drug effects


  • Antiviral Agents
  • Viral Nonstructural Proteins
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases