Abstract: foods Article In Vitro Determination of Inhibitory Effects of Humic Substances Complexing Zn and Se on SARS-CoV-2 Virus Replication Polett Hajdrik 1,† , Bernadett Pályi 2,† , Zoltán Kis 2,3 , Noémi Kovács 1,4 , Dániel Sándor Veres 1 , Krisztián Szigeti 1 , Ferenc Budán 5,6 , Imre Hegedüs 1 , Tibor Kovács 7 , Ralf Bergmann 1,8 and Domokos Máthé 1,4,9, * 1 2 3 4 5 6 7 8 9



 Citation: Hajdrik, P.; Pályi, B.; Kis, Z.; * † Department of Biophysics and Radiation Biology, Semmelweis University, Üllői út 26., H-1085 Budapest, Hungary; h.polett0809@gmail.com (P.H.); kovacsnoi@hotmail.com (N.K.); veres.daniel@med.semmelweis-univ.hu (D.S.V.); krisztian.szigeti@gmail.com (K.S.); hegedus.imre1@med.semmelweis-univ.hu (I.H.); rkbergmann@web.de (R.B.) National Biosafety Laboratory, National Public Health Center, Albert Flórián út 2-6, H-1097 Budapest, Hungary; palyi.bernadett@nnk.gov.hu (B.P.); kis.zoltan@nnk.gov.hu (Z.K.) Department of Microbiology, Semmelweis University, Üllői út 26., H-1085 Budapest, Hungary CROmed Translational Research Ltd., Tűzoltó u. 37-47, H-1094 Budapest, Hungary Institute of Transdisciplinary Discoveries, Medical School, University of Pécs, Ifjúság útja 11, H-7624 Pécs, Hungary; budfer2@gmail.com Institute of Physiology, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary Institute of Radiochemistry and Radioecology, University of Pannonia, Egyetem u. 10., H-8200 Veszprem, Hungary; kovacstiborjanos@gmail.com Helmholtz-Zentrum Dresden Rossendorf, Bautzner Landstraße 400, 01328 Dresden, Germany Hungarian Centre of Excellence for Molecular Medicine, In Vivo Imaging Advanced Core Facility, Semmelweis University Site, Római Blvd. 21, H-6723 Szeged, Hungary Correspondence: domokos.mathe@hcemm.eu These authors contributed equally to this work. Kovács, N.; Veres, D.S.; Szigeti, K.; Budán, F.; Hegedüs, I.; Kovács, T.; Bergmann, R.; et al. In Vitro Determination of Inhibitory Effects of Humic Substances Complexing Zn and Se on SARS-CoV-2 Virus Replication. Foods 2022, 11, 694. https://doi.org/10.3390/ foods11050694 Academic Editors: Maria Luisa Serralheiro and Rita Isabel Pacheco Received: 31 January 2022 Accepted: 23 February 2022 Published: 26 February 2022 Abstract: (1) Background: Humic substances are well-known human nutritional supplement materials and they play an important performance-enhancing role as animal feed additives. For decades, ingredients of humic substances have been proven to carry potent antiviral effects against different viruses. (2) Methods: Here, the antiviral activity of a humic substance containing ascorbic acid, Se− and Zn2+ ions intended as a nutritional supplement material was investigated against SARS-CoV-2 virus B1.1.7 Variant of Concern (“Alpha Variant”) in a VeroE6 cell line. (3) Results: This combination has a significant in vitro antiviral effect at a very low concentration range of its intended active ingredients. (4) Conclusions: Even picomolar concentration ranges of humic substances, Vitamin C and Zn/Se ions in the given composition, were enough to achieve 50% viral replication inhibition in the applied SARS-CoV-2 virus inhibition test. Keywords: SARS-CoV-2; humic acid; fulvic acid; Zn-Se-ascorbic acid complex; antiviral activity; RT-PCR Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil-