Abstract: INTERNATIONAL JOURNAL OF MOlecular medicine 47: 326-334, 2021 326 Zinc and SARS‑CoV‑2: A molecular modeling study of Zn interactions with RNA‑dependent RNA‑polymerase and 3C‑like proteinase enzymes ALI PORMOHAMMAD, NADIA K. MONYCH and RAYMOND J. TURNER Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N4V8, Canada Received May 27, 2020; Accepted October 13, 2020 DOI: 10.3892/ijmm.2020.4790 Abstract. RNA‑dependent RNA‑polymerase (RdRp) and 3C‑like proteinase (3CLpro) are two main enzymes that play a key role in the replication of SARS‑CoV‑2. Zinc (Zn) has strong immunogenic properties and is known to bind to a number of proteins, modulating their activities. Zn also has a history of use in viral infection control. Thus, the present study models potential Zn binding to RdRp and the 3CLpro. Through molecular modeling, the Zn binding sites in the aforementioned two important enzymes of viral replication were found to be conserved between severe acute respiratory syndrome (SARS)‑coronavirus (CoV) and SARS‑CoV‑2. The location of these sites may influence the enzymatic activity of 3CLpro and RdRp in coronavirus disease 2019 (COVID‑19). Since Zn has established immune health benefits, is readily available, non‑expensive and a safe food supplement, with the comparisons presented here between SARS‑CoV and COVID‑19, the present study proposes that Zn could help ameliorate the disease process of COVID‑19 infection.