Understanding SARS-CoV-2 endocytosis for COVID-19 drug repurposing

Oleg O Glebov, Oleg O Glebov

Abstract

The quest for the effective treatment against coronavirus disease 2019 pneumonia caused by the severe acute respiratory syndrome (SARS)-coronavirus 2(CoV-2) coronavirus is hampered by the lack of knowledge concerning the basic cell biology of the infection. Given that most viruses use endocytosis to enter the host cell, mechanistic investigation of SARS-CoV-2 infection needs to consider the diversity of endocytic pathways available for SARS-CoV-2 entry in the human lung epithelium. Taking advantage of the well-established methodology of membrane trafficking studies, this research direction allows for the rapid characterisation of the key cell biological mechanism(s) responsible for SARS-CoV-2 infection. Furthermore, 11 clinically approved generic drugs are identified as potential candidates for repurposing as blockers of several potential routes for SARS-CoV-2 endocytosis. More broadly, the paradigm of targeting a fundamental aspect of human cell biology to protect against infection may be advantageous in the context of future pandemic outbreaks.

Keywords: COVID-19; SARS-CoV-2; drug repurposing; endocytosis; membrane trafficking.

Conflict of interest statement

The authors declare no conflict of interest.

© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Figures

Fig. 1
Fig. 1
A simplified representation of endocytic pathways potentially involved in internalisation of SARS‐CoV‐2. Selected endocytic pathways are enclosed in grey boxes. Selected key structural and regulatory proteins are shown graphically or mentioned by name. Thick arrows represent the directional flow of membrane trafficking pathways. A thin black arrow represents viral trajectory following the completion of its putative endocytic itinerary. Red lines with squares at their ends indicate putative pharmacological blockade of processes. Black line with a square at its end indicates the suggested effect of chloroquine and hydroxychloroquine on viral fusion in the endosome. The names of the candidate drug blockers are italicised.

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