Abstract: Journal Pre-proofs In vitro Potential Antiviral SARS-CoV-19- Activity of Natural Product Thymohydroquinone and Dithymoquinone from Nigela sativia Eman R. Esharkawy, Faisal Almalki, Taibi Ben Hadda PII: DOI: Reference: S0045-2068(21)00965-2 https://doi.org/10.1016/j.bioorg.2021.105587 YBIOO 105587 To appear in: Bioorganic Chemistry Received Date: Revised Date: Accepted Date: 29 June 2021 19 December 2021 26 December 2021 Please cite this article as: E.R. Esharkawy, F. Almalki, T. Ben Hadda, In vitro Potential Antiviral SARS-CoV-19Activity of Natural Product Thymohydroquinone and Dithymoquinone from Nigela sativia, Bioorganic Chemistry (2021), doi: https://doi.org/10.1016/j.bioorg.2021.105587 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2021 Published by Elsevier Inc. In vitro Potential Antiviral SARS-CoV-19- Activity of Natural Product Thymohydroquinone and Dithymoquinone from Nigela sativia Eman R. Esharkawy*1,2, Faisal Almalki3 , Taibi Ben Hadda,3,4 1Department of Chemistry, Science Faculty, Northern Border University, ARAR, North Region, Saudi Arabia. 2Department of Plant Ecology and Range Management, Ecology and Dry Lands Agriculture Division, Desert Research Center, Mathef El-Mataria, 15753, Egypt. 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm AlQura University, Makkah 21955, Saudi Arabia. 4Laboratory of Applied Chemistry & Environment, Faculty of Sciences, Mohammed Premier University, MB 524, 60000 Oujda, Morocco. Corresponding author: elsharqawyeman2017@gmail.com Abstract: Inflammation, oxidation, and compromised immunity all increase the dangers of COVID-19, whereas many pharmaceutical protocols may lead to increased immunity such as ingesting from sources containing vitamin E and zinc. A global search for natural remedies to fight COVID-19 has emerged, to assist in the treatment of this infamous coronavirus. Nigella satvia is a worldrenowned plant, an esteemed herbal remedy, which can be used as a liquid medicine to increase immunity while decreasing the dangers of acute respiratory distress syndrome. Thymoqinone (TQ), dithymoqinone (DTQ) and thymohydroquinone (THQ), are major compounds of the essential oil contained in N.sativa. A current study aims to discover the antiviral activity of two compounds, Thymohydroquinone and Dithymoquinone, which are synthesized through simple chemical procedures, deriving from thymoquinone, which happens to be a major compound of Nigella sativa. A half-maximal cytotoxic concentration, “CC50”, was calculated by MTT assay for each individual drug, The sample showed anti-SARS-CoV-2 activity at non-cytotoxic 1 nanomolar concentrations in vitro with a low selectivity index (CC50/IC50 = 31.74/23.15=1.4), whereby Dimthymoquinone shows high cytotoxicity. Keywords: Antiviral, SARSCoV-19, thymoquinon, Dithemoquinone , hydrothymoquinone