Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who devel...

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Bibliographic Details
Published in:bioRxiv 2021-03
Main Authors: Ordonez, Alvaro A, Bullen, Cynthia K, Villabona-Rueda, Andres F, Thompson, Elizabeth A, Turner, Mitchell L, Davis, Stephanie L, Komm, Oliver, Powell, Jonathan D, D'alessio, Franco R, Yolken, Robert H, Jain, Sanjay K, Jones-Brando, Lorraine
Format: Article
Language:English
Subjects:
Antiviral activity
Cell activation
Coronaviridae
Coronaviruses
COVID-19
Cytokines
Infections
Lungs
Lymphocytes T
Myeloid cells
Pandemics
Patent applications
Prophylaxis
Public health
Respiratory tract
Severe acute respiratory syndrome coronavirus 2
Sulforaphane
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Summary:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection or treatment of early disease. Competing Interest Statement LJ-B, AAO, RHY, and SKJ are co-inventors on pending patent application USPA #63/142,598, Methods for inhibiting coronaviruses using sulforaphane filed by Johns Hopkins University.
DOI:10.1101/2021.03.25.437060