Unveiling the Silent Antiviral Effectors Fighting Against COVID-19

Abstract

The host cell receptors and associated anti-viral genes mediating SARS-CoV-2 infections are still elusive. Here, we show that COVID-19 patients compared with healthy donors, display discrepancies regarding up-regulation of ACE2 and TMPRSS2. Further, we have screened in these samples key players associated with the antiviral response: MX1, IRF3, HMOX1 and ADAM17. Strikingly, results show that COVID-19 patients present a distinct pattern of expression for these molecules which could account for infection. Using single-cell sequencing data, we demonstrate that MX1, the main IFN-induced molecule restricting influenza (IAV) infection, is expressed in goblet and ciliated cells in the respiratory tract of healthy human tissue. We reveal that, MX1 expression is triggered by SARS-CoV-2. Furthermore, we showcase that MX1 can be modulated by androgen deprivation therapy or hemin, a potent inducer of HMOX1. Taken together, these results point out to an alternative druggable target that can halt SARS-CoV-2 infection.

Funding: This work was supported by grants from AGENCIA-PICT-2015-1786 (Argentina); AGENCIA-PICT-2016-1366 (Argentina); AGENCIA-PICT-2016-0056 (Argentina), UBACyT 2018-20020170100585BA (Argentina); AGENCIA-PICT-RAICES-2018-02639 (Argentina).

Conflict of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Keywords: SARS-CoV-2, COVID-19, MX1, HMOX1, lung, prostate, androgen deprivation therapy (ADT), hemin