The cranberry extract Oximacro® prevents Hazara virus infection by inhibiting the attachment to target cells

Hazara virus (HAZV) belongs to the Nairoviridae family and is included in the same serogroup of the Crimean-Congo haemorrhagic fever virus (CCHFV). CCHFV is the most widespread tick-borne arbovirus responsible for a serious haemorrhagic disease for which specific and effective treatment or preventive system are missing. Bioactive compounds derived from several natural products may provide a natural source of broad-spectrum antiviral agents and, in addition, provided by a good tolerability and minimal side effects. Previous in vitro studies showed that Oximacro®, a cranberry (V. macrocarpon Ait.) extract with a high polyphenol content, inhibits the replication of herpes simplex and influenza viruses by hampering their attachment to target cells. Given the broad-spectrum antimicrobial activity of polyphenols and the urgency to develop therapies for the treatment of CCHF, we investigated the antiviral activity of Oximacro® against the Hazara virus (HAZV), a surrogate nairovirus model of CCHFV that can be handled in Level 2 Biosecurity Laboratories (BSL-2). The results of time-of-addition experiments indicated that Oximacro ® exerts an antiviral activity against HAZV by targeting early stages of the viral replication cycle, such as the initial adsorption to target cells. Although the details of the molecular mechanism of action remain to be clarified, Oximacro® exerts a virucidal effect through a direct interaction with HAZV particles that leads to the subsequent impairment of virus attachment to cell-surface receptors. As a whole, the evidence obtained suggest Oximacro® as a valuable candidate to be considered for the development of therapeutic strategies for CCHF infections.