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

Abstract

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.

A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids

“…ACE2-ABD, when bound to albumin, might direct the complex into the FcRn-mediated recycling pathway, which would be away from the lysosome-endosome pathway that seems crucial for viral processing and replication. 42 This may provide a theoretical advantage for our ACE2 1-618 protein fused with ABD over the naked ACE2 1-740 protein.…”

Lysosomotropic Features and Autophagy Modulators among Medical Drugs: Evaluation of Their Role in Pathologies

“…Schneider et al, 1997 [5]; Pisonero-Vaquero, Medina, 2017 [2] Carrière et al, 2020 [6] Blaess et al, 2020 [7] Norinder et al, 2020 [8] Hydroxychloroquine, antiviral effect in vitro, similar to chloroquine. The in vivo efficacy of hydroxychloroquine in the treatment of COVID-19 is currently a matter of debate.…”

“…Carrière et al, 2020 [6] Blaess et al, 2020 [7] Norinder et al, 2020 [8] Triton WR 1339 (Tyloxapol), non-ionic surfactant, additive in pharmacy; PEGylated Tyloxapol niosomes for the controlled release of first-line anti-tuberculosis drugs.…”

Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19

“…Lately, lysosomes have gained increasing attention in drug repurposing since they are considered to function as the key cell organelle involved in the SARS-CoV-2 infection of nasal and pulmonary tissue [ 2 , 3 , 4 , 5 , 6 ]. Repurposing of approved active compounds, with particular regard to their metabolites accumulating in the lysosomes of pulmonary tissue and mononuclear cells, could be a strategy to bridge this gap and to achieve a better outcome, unlike (hydroxy) chloroquine administration in COVID-19 [ 1 ] and SARS [ 7 ].…”