The SARS-CoV-2-Inactivating Activity of Hydroxytyrosol-Rich Aqueous Olive Pulp Extract (HIDROX®) and Its Use as a Virucidal Cream for Topical Application

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Although measures to control SARS-CoV-2, namely, vaccination, medication, and chemical disinfectants are being investigated, there is an increase in the demand for auxiliary antiviral approaches using natural compounds. Here we have focused on hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX®) and evaluated its SARS-CoV-2-inactivating activity in vitro. We showed that the HIDROX solution exhibits time- and concentration-dependent SARS-CoV-2-inactivating activities, and that HIDROX has more potent virucidal activity than pure HT. The evaluation of the mechanism of action suggested that both HIDROX and HT induced structural changes in SARS-CoV-2, which changed the molecular weight of the spike proteins. Even though the spike protein is highly glycosylated, this change was induced regardless of the glycosylation status. In addition, HIDROX or HT treatment disrupted the viral genome. Moreover, the HIDROX-containing cream applied on film showed time- and concentration-dependent SARS-CoV-2-inactivating activities. Thus, the HIDROX-containing cream can be applied topically as an antiviral hand cream. Our findings suggest that HIDROX contributes to improving SARS-CoV-2 control measures.

Health benefits of olive oil and by-products and possible innovative applications for industrial processes

“…Lately, it has been shown that oleuropein and HT in extracts obtained from leaves or OWW, respectively, display antiviral activities against the SARS-COV2, possibly by inducing structural changes of the virus [26][27]. Hydrogel or cream enriched with HT has been proposed as an antiviral hand cream [26].…”

“…Lately, it has been shown that oleuropein and HT in extracts obtained from leaves or OWW, respectively, display antiviral activities against the SARS-COV2, possibly by inducing structural changes of the virus [26][27]. Hydrogel or cream enriched with HT has been proposed as an antiviral hand cream [26]. On another hand, it has been proposed that phytosomal formulation containing luteolin (in olive pomace oil) may mitigate some of the symptoms observed in long-COVID patients [28].…”

A Review on SARS-CoV-2-Induced Neuroinflammation, Neurodevelopmental Complications, and Recent Updates on the Vaccine Development

“…As mitochondria-mediated aging is associated with dysregulated metabolism and requires novel therapeutic modalities viz., mitochondrial anti-oxidants and anti-inflammatory molecules are likely to correct these dysregulated metabolic and physiological processes before the administration of vaccines against SARS-CoV-2-induced neuropathology [123]. "Hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX®)" has been reported to mitigate SARS-CoV-2-induced pathophysiology by inducing potent virucidal activity [124]. Hydroxytyrosol (HT) and oleuropein aglycone (OLE) are two potential molecules reported being beneficial to mitigate the pathophysiology of neurodegeneration [124].…”

“…"Hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX®)" has been reported to mitigate SARS-CoV-2-induced pathophysiology by inducing potent virucidal activity [124]. Hydroxytyrosol (HT) and oleuropein aglycone (OLE) are two potential molecules reported being beneficial to mitigate the pathophysiology of neurodegeneration [124]. Hormesis and anti-oxidant nature, which enhances the activity of proteasome and phase II detoxifying enzymes, are potential mechanisms of action by which these pharmacological molecules work against SARS-CoV-2-induced neuropathophysiology [125,126].…”

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

“…Other antiviral mechanisms proposed by some authors against SARS-CoV-2 observed in antioxidant compounds are: (a) inhibition of the viral replication (i.e., curcumin and resveratrol) [ 239 , 240 ], (b) blockage of the inflammatory response (i.e., resveratrol, curcumin, naringenin, and N-acetil cysteine) [ 207 , 239 , 240 , 241 ], (c) inhibition of SARS-CoV-2 fusion/entry by interaction with SARS-CoV-2:ACE-2 interface (luteolin and dithymoquinone) [ 242 , 243 ], (d) as radical scavengers (i.e., methide quinone celastrol as superoxide radical scavenger or hydrogen as hydroxyl radical scavenger) [ 214 , 244 ], (e) inhibition of ACE activity (N-acetyl cysteine) [ 245 ], (f) modulation of endoplasmic reticulum stress (andrographolide and melatonin) [ 246 ], (g) activation of Nrf2 pathway (antioxidant mixture PB125 ® ) [ 247 ], (h) antithromboembolics (hesperidin and diosmin mixture) [ 248 ], and (i) inducing aggregation of SARS-CoV-2 spike proteins and disruption of the viral genome (hydroxytyrosol) [ 249 ]. Figure 2 shows the mechanisms of antioxidants compounds that could prevent neuronal damage in patients with COVID-19…”