In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.

Department of Chemistry Borujerd Branch Islamic Azad University Borujerd Iran

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove Czech Republic

Department of Chemistry Federal Institute of Espirito Santo Vila Velha ES Brazil

Graduate Program in Chemistry Federal University of Espirito Santo Vitoria ES Brazil

Independent Researcher Montreal QC Canada

Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense Military Institute of Engineering Rio de Janeiro RJ Brazil

Université de Québec INRS Centre Armand Frappier Santé Biotechnologie 531 Boulevard Des Prairies Laval Québec H7V 1B7 Canada

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Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2