Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells

Rafael R G Machado; Talita Glaser; Danielle B Araujo; Lyvia Lintzmaier Petiz; Danielle B L Oliveira; Giuliana S Durigon; Alessandra L Leal; João Renato R Pinho; Luis C S Ferreira; Henning Ulrich; Edison L Durigon; Cristiane Rodrigues Guzzo

doi:10.1021/acsptsci.1c00080

Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells

ACS Pharmacol Transl Sci. 2021 Sep 3;4(5):1514-1527. doi: 10.1021/acsptsci.1c00080. eCollection 2021 Oct 8.

Authors

Rafael R G Machado¹, Talita Glaser², Danielle B Araujo^{1

3}, Lyvia Lintzmaier Petiz², Danielle B L Oliveira^{1

3

4}, Giuliana S Durigon⁵, Alessandra L Leal⁶, João Renato R Pinho^{3

7

8}, Luis C S Ferreira^{1

9}, Henning Ulrich², Edison L Durigon^{1

9}, Cristiane Rodrigues Guzzo¹

Affiliations

¹ Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508, Brazil.
² Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508, Brazil.
³ Hospital Israelita Albert Einstein, São Paulo 05652, Brazil.
⁴ Development and Innovation Center, Laboratory of Virology, Butantan Institute, São Paulo 05503, Brazil.
⁵ Medical School Clinical Hospital, University of São Paulo, São Paulo 05508, Brazil.
⁶ Gaspar Vianna Clinic Hospital Foundation, Belém 66083, Brazil.
⁷ LIM-03, Central Laboratories Division, Clinics Hospital, São Paulo School of Medicine, University of São Paulo, São Paulo 05508, Brazil.
⁸ LIM-07, Institute of Tropical Medicine, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo 05508, Brazil.
⁹ Scientific Platform Pasteur USP, São Paulo 05508, Brazil.

Abstract

An unprecedented global health crisis has been caused by a new virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed experiments to test if a hypertonic saline solution was capable of inhibiting virus replication. Our data show that 1.2% NaCl inhibited virus replication by 90%, achieving 100% of inhibition at 1.5% in the nonhuman primate kidney cell line Vero, and 1.1% of NaCl was sufficient to inhibit the virus replication by 88% in human epithelial lung cell line Calu-3. Furthermore, our results indicate that the inhibition is due to an intracellular mechanism and not to the dissociation of the spike SARS-CoV-2 protein and its human receptor. NaCl depolarizes the plasma membrane causing a low energy state (high ADP/ATP concentration ratio) without impairing mitochondrial function, supposedly associated with the inhibition of the SARS-CoV-2 life cycle. Membrane depolarization and intracellular energy deprivation are possible mechanisms by which the hypertonic saline solution efficiently prevents virus replication in vitro assays.