The appearance of new respiratory virus infections in humans with epidemic or pandemic potential has underscored the urgent need for effective broad-spectrum antivirals (BSAs). Bioactive compounds derived from plants may provide a natural source of new BSA candidates. Here, we investigated the novel phytocomplex formulation SP4™ as a candidate direct-acting BSA against major current human respiratory viruses, including coronaviruses and influenza viruses. SP4™ inhibited the in vitro replication of SARS-CoV-2, hCoV-OC43, hCoV-229E, Influenza A and B viruses, and respiratory syncytial virus in the low-microgram range. Using hCoV-OC43 as a representative respiratory virus, most of the antiviral activity of SP4™ was observed to stem primarily from its dimeric A-type proanthocyanidin (PAC-A) component. Further investigations of the mechanistic mode of action showed SP4™ and its PAC-A-rich fraction to prevent hCoV-OC43 from attaching to target cells and exert virucidal activity. This occurred through their interaction with the spike protein of hCoV-OC43 and SARS-CoV-2, thereby interfering with spike functions and leading to the loss of virion infectivity. Overall, these findings support the further development of SP4™ as a candidate BSA of a natural origin for the prevention of human respiratory virus infections.

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.

Cranberry (Vaccinium macrocarpon) is a distinctive source of polyphenols as flavonoids and phenolic acids that has been described to display beneficial effects against urinary tract infections (UTIs), the second most common type of infections worldwide. UTIs can lead to significant morbidity, especially in healthy females due to high rates of recurrence and antibiotic resistance. Strategies and therapeutic alternatives to antibiotics for prophylaxis and treatment against UTIs are continuously being sought after. Different to cranberry, which have been widely recommended in traditional medicine for UTIs prophylaxis, probiotics have emerged as a new alternative to the use of antibiotics against these infections and are the subject of new research in this area. Besides uropathogenic Escherichia coli (UPEC), the most common bacteria causing uncomplicated UTIs, other etiological agents, such as Klebsiellapneumoniae or Gram-positive bacteria of Enterococcus and Staphylococcus genera, seem to be more widespread than previously appreciated. Considerable current effort is also devoted to the still-unraveled mechanisms that are behind the UTI-protective effects of cranberry, probiotics and their new combined formulations. All these current topics in the understanding of the protective effects of cranberry against UTIs are reviewed in this paper. Further progresses expected in the coming years in these fields are also discussed.

Yak-Kong (YK) (Glycine max), a small black soybean cultivar with a green embryo, was evaluated for functional constituents with a focus on atherosclerosis prevention. In comparison to common yellow and black soybean cultivars, YK contains significantly higher concentrations of antioxidants, particularly in its seed coat. A comprehensive phenolic composition analysis revealed that proanthocyanidins were the major phenolic group in YK. In contrast to other proanthocyanidin-rich foods, YK was rich in bioavailable proanthocyanidins (with a degree of polymerization ≤3) specifically with A-type dimers. Significant concentrations of phloridzin and coumestrol were also exclusively found in YK seed coat and the embryo, respectively. Extracts of both the proanthocyanidin-rich seed coat and isoflavonoid-rich embryo of YK attenuated adhesion of THP-1 to LPS-stimulated human umbilical vascular endothelial cells, suggesting that they are important sources of coronary heart disease-preventive phenolics. YK has promising potential for further development as a functional food source targeted at atherosclerosis prevention.

In the absence of efficient preventive vaccines, topical microbicides offer an attractive alternative in the prevention of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Because of their recognized anti-adhesive activity against bacterial pathogens, cranberry (Vaccinium macrocarpon Ait.) extracts may represent a natural source of new antiviral microbicides. However, few studies have addressed the applications of cranberry extract as a direct-acting antiviral agent. Here, we report on the ability of the novel cranberry extract Oximacro(®) and its purified A-type proanthocyanidins (PACs-A), to inhibit HSV-1 and HSV-2 replication in vitro. Analysis of the mode of action revealed that Oximacro(®) prevents adsorption of HSV-1 and HSV-2 to target cells. Further mechanistic studies confirmed that Oximacro(®) and its PACs-A target the viral envelope glycoproteins gD and gB, thus resulting in the loss of infectivity of HSV particles. Moreover, Oximacro(®) completely retained its anti-HSV activity even at acidic pHs (3.0 and 4.0) and in the presence of 10% human serum proteins; conditions that mimic the physiological properties of the vagina - a potential therapeutic location for Oximacro(®). Taken together, these findings indicate Oximacro(®) as an attractive candidate for the development of novel microbicides of natural origin for the prevention of HSV infections.