Propolis and its potential against SARS-CoV-2 infection mechanisms and COVID-19 disease: Running title: Propolis against SARS-CoV-2 infection and COVID-19
Authors: Andresa Aparecida Berretta
David De Jong
José Manuel Cóndor Capcha
Marcelo Augusto Duarte Silveira
Journal: Biomedicine & Pharmacotherapy (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Anti-inflammatory; Antiviral; COVID-19; PAK1 blocker; Propolis
Affiliations: Research, Development and Innovation Department, Apis Flora Indl. Coml. Ltda, Ribeirão Preto, São Paulo, Brazil. Electronic address: ., Interdisciplinary Stem Cell Institute at Miller School of Medicine, University of Miami, Miami, Florida, United States. Electronic address: ., Genetics Department, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: .

Abstract:  Propolis, a resinous material produced by honey bees from plant exudates, has long been used in traditional herbal medicine and is widely consumed as a health aid and immune system booster. The COVID-19 pandemic has renewed interest in propolis products worldwide; fortunately, various aspects of the SARS-CoV-2 infection mechanism are potential targets for propolis compounds. SARS-CoV-2 entry into host cells is characterized by viral spike protein interaction with cellular angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2. This mechanism involves PAK1 overexpression, which is a kinase that mediates coronavirus-induced lung inflammation, fibrosis, and immune system suppression. Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo. In pre-clinical studies, propolis promoted immunoregulation of pro-inflammatory cytokines, including reduction in IL-6, IL-1 beta and TNF-α. This immunoregulation involves monocytes and macrophages, as well as Jak2/STAT3, NF-kB, and inflammasome pathways, reducing the risk of cytokine storm syndrome, a major mortality factor in advanced COVID-19 disease. Propolis has also shown promise as an aid in the treatment of various of the comorbidities that are particularly dangerous in COVID-19 patients, including respiratory diseases, hypertension, diabetes, and cancer. Standardized propolis products with consistent bioactive properties are now available. Given the current emergency caused by the COVID-19 pandemic and limited therapeutic options, propolis is presented as a promising and relevant therapeutic option that is safe, easy to administrate orally and is readily available as a natural supplement and functional food. 

Retracted: No

PubPeer comments:
 The 1st author is affiliated with Apis Flora Indl. Coml. Ltda, the producer of propolis. Why is not a conflict of interest declared? , 
 #1 At the end of the paper, this is made clear. Conflict of interest statement Dr. Berretta is an employee of Apis Flora. , 
 Sorry, that comment had to do with the clinical trial paper. https: doi.org 10.1016 j.biopha.2021.111526 the review paper you refer to was a general review of the potential benefits of propolis. The company did not support that paper in any way, nor did it fund the publication fees. There was no declaration of conflict of interests based on examples from other publications in the journal and in other journals. Also, the author clearly indicated her company address, so that no attempt was made to hide the fact that she works for Apis Flora. The clinical trial results research was partially financed by Apis Flora, so a conflict of interests statement was made. ,