SARS-CoV-2 replicates efficiently in the upper airways during the prodromal stage, resulting in environmental viral shedding from patients with active COVID-19 as well as from asymptomatic individuals. There is a need to find pharmacological interventions to mitigate the spread of COVID-19. Hypothiocyanite and lactoferrin are molecules of the innate immune system with a large spectrum cidal activity. The Food and Drug Administration and the European Medicines Agency designated the hypothiocyanite and lactoferrin combination as an orphan drug. We report an in vitro study showing that micromolar concentrations of hypothiocyanite exhibit dose- and time-dependent virucidal activity against SARS-CoV-2 and that the latter is slightly enhanced by the simultaneous presence of lactoferrin.

Hazara virus (HAZV) belongs to the Nairoviridae family and is included in the same serogroup of the Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is the most widespread tick-borne arbovirus. It is responsible for a serious hemorrhagic disease, for which specific and effective treatment and preventive systems are missing. Bioactive compounds derived from several natural products may provide a natural source of broad-spectrum antiviral agents, characterized by good tolerability and minimal side effects. Previous in vitro studies have shown that a cranberry (Vaccinium macrocarpon Ait.) extract containing a high content of A-type proanthocyanidins (PAC-A) 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 cranberry extract against HAZV, a surrogate nairovirus model of CCHFV that can be handled in Level 2 Biosafety Laboratories (BSL-2). The results indicate that the cranberry extract exerts an antiviral activity against HAZV by targeting early stages of the viral replication cycle, including the initial adsorption to target cells. Although the details of the molecular mechanism of action remain to be clarified, the cranberry extract exerts a virucidal effect through a direct interaction with HAZV particles that leads to the subsequent impairment of virus attachment to cell-surface receptors. Finally, the antiviral activity of the cranberry extract was also confirmed for CCHFV. As a whole, the evidence obtained suggests that cranberry extract is a valuable candidate to be considered for the development of therapeutic strategies for CCHFV infections.

The Ebola virus (EBOV) and the Rabies virus (RABV) are deadly infectious agents impacting human and animal health. Current prevention and control strategies mainly rely on vaccines and antibodies, highlighting the urgent need for effective, low-cost antivirals suitable for therapeutic options. Plant-derived bioactive compounds offer a promising natural source for such candidate antivirals. As a contribution to this antiviral approach, we have characterized the anti-EBOV and anti-RABV activity of a Cranberry extract (CE) endowed with a very high content of bioactive A2-type proanthocyanidin (PAC-A2). The CE inhibited the in vitro infection of both pseudoviruses expressing EBOV-GP or RABV-G glycoproteins and authentic EBOV and RABV. Attachment and entry assays revealed that the extract targets early phases of infection preventing attachment and entry. Noteworthy, synthetic PAC-A2 reproduced the antiviral activity observed with the whole CE. Mechanistic studies then revealed that the CE interacted directly with the ectodomain of EBOV-GP or the RABV-G, suggesting interference with their functions. In support to this hypothesis, fluorescence spectroscopy analysis showed a reduction in intrinsic fluorescence of both EBOV-GP and RABV-G after incubation with synthetic PAC-A2, thus confirming a direct interaction of the viral glycoproteins with PAC-A2. In silico docking simulations further sustained in vitro results by predicting the binding of PAC-A2 into the binding pocket of EBOV-GP and to the trimeric architecture of RABV-G. Together, these results suggest this cranberry extract and bioactive PAC-A2 as potential candidates to be further develop as novel antiviral agents for the prevention of EBOV and RABV infections.