Hemin shows antiviral activity in vitro, possibly through suppression of viral entry mediators

Abstract

Heme oxygenase-1 (HO-1) is a stress-induced enzyme that catalyzes the breakdown of heme into biliverdin, carbon monoxide, and iron. Targeting HO-1 to treat severe COVID-19 has been suggested by several groups, yet the role of HO-1 in SARS-CoV-2 infection remains unclear. Based on this, we aimed to investigate the antiviral activity of Hemin, an activator of HO-1. Infectivity of SARS-CoV-2 was decreased in Vero E6 cells treated with Hemin. Hemin also decreased TMPRSS2 and ACE2 mRNA levels in non-infected cells, possibly explaining the observed decrease in infectivity. TMPRSS2 protein expression and proteolytic activity were decreased in Vero E6 cells treated with Hemin. Besides that, experimental studies supported with in silico calculations. Overall, our study supports further exploration of Hemin as a potential antiviral and inflammatory drug for the treatment of COVID-19.

Host and viral proteins involved in SARS‐CoV‐2 infection differentially bind heme

“…Thus, as described for other viruses, such as human immunodeficiency virus 1 24 and Zika virus, 25,26 a potential heme‐driven effect in COVID‐19 infections has been discussed and analyzed in vitro with contradicting results. While heme has been shown to inhibit SARS‐CoV‐2 attachment to endothelial cells and/or intracellular replication in kidney epithelial cells in a dose‐dependent manner, which was mainly attributed to heme‐driven upregulation of heme oxygenase 1 expression, 27–29 an antiviral potency of heme toward SARS‐CoV‐2 infection has been disproven by others as demonstrated in kidney and airway epithelial cell lines 30 . Beyond an impact of heme on the attachment and replication of SARS‐CoV‐2, direct interaction of heme with SARS‐CoV‐2 proteins of the intra‐ and extravirion (i.e., spike glycoprotein, 20,28,31 nucleoprotein, 28 membrane protein, 28 the nonstructural proteins [NSP] 3 and 7, 28 and protein 7a 20 ) as well as heme binding to the in SARS‐CoV‐2 infection participating human host cell proteins TMPRSS2 and ACE2 20 has been proposed.…”