Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs?

Version 1 : Received: 5 April 2020 / Approved: 7 April 2020 / Online: 7 April 2020 (11:02:13 CEST)

A peer-reviewed article of this Preprint also exists.

Barrantes FJ (2020) While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs? Front. Physiol. 11:820. doi: 10.3389/fphys.2020.00820 Barrantes FJ (2020) While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs? Front. Physiol. 11:820. doi: 10.3389/fphys.2020.00820

Journal reference: Frontiers in Physiology 2020, 11
DOI: 10.3389/fphys.2020.00820

Abstract

At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.

Subject Areas

Coronavirus; COVID-19; SARS-CoV-2; design drugs; ACE2; prophylaxis

Comments (1)

Comment 1
Received: 28 April 2020
Commenter: Dr Vinod Nikhra, M.D.
The commenter has declared there is no conflict of interests.
Comment: The review article is very informative. The author is right that getting an effective vaccine may take an uncertain time. I liked the approach to the issue of dealing with Covid-19 through developing potentially useful agents in perspective of latest understanding of its pathogenesis. The various approaches discussed with their rationale, make an interesting reading.
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