A mixture of essential oils from three Cretan Aromatic Plants (thyme, Greek sage and Cretan dittany, CAPeo) inhibits SASR-CoV-2 proliferation:in vitroevidence and a Proof-of-Concept intervention study in mild ambulatory COVID-19-positive patients

The need for therapeutic regimens for the non-critically ill patients of the COVID-19 pandemic remains unmet. In this line, repurposing existing drugs, against known or predicted SARS-CoV-2 protein actions, has been advanced, while natural products have also been tested. Previous work has shown that a Cretan Aromatic Plant (Thymbra capitata(L.) Cav.,Salvia fruticosaMill. andOriganum dictamnusL.) essential oil mixture (CAPeo) has a remarkablein vitroantiviral activity against Influenza A & B and Rhinovirus 14 strains, decreasing the symptoms of upper respiratory tract infections, while proven safe in experimental animals and humans. Here, we tested CAPeo in VERO cells infected with SASR-CoV-2. We report that this mixture, at similar concentrations as those previously reported, exhibits a remarkable antiviral activity. Administration of 1 ml of a 1.5% CAPeo in olive oil, in a Proof-of-Concept intervention study in SARS-CoV-2-positive, exhibiting mild COVID-19 symptoms, humans resulted in a significant amelioration of general and local symptoms of the disease. We conclude that CAPeo may be a valuable addition for the prevention and/or treatment of mild COVID-19 ambulatory patients, pending a confirmation through a prospective randomized controlled trial in humans (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04705753">NCT04705753</ext-link>).