plants Review Sterols and Triterpenes: Antiviral Potential Supported by In-Silico Analysis Nourhan Hisham Shady 1,† , Khayrya A. Youssif 2,† , Ahmed M. Sayed 3 , Lassaad Belbahri 4 , Tomasz Oszako 5 , Hossam M. Hassan 3,6 and Usama Ramadan Abdelmohsen 1,7, *   Citation: Hisham Shady, N.; Youssif, K.A.; Sayed, A.M.; Belbahri, L.; Oszako, T.; Hassan, H.M.; Abdelmohsen, U.R. Sterols and Triterpenes: Antiviral Potential Supported by In-Silico Analysis. Plants 2021, 10, 41. https:// dx.doi.org/10.3390/plants10010041 Received: 3 December 2020 Accepted: 19 December 2020 Published: 26 December 2020 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2020 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/). 1 Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, P.O. Box 61111, New Minia City, Minia 61519, Egypt; noura_shady2013@yahoo.com 2 Department of Pharmacognosy, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11865, Egypt; khayrya.youssif@gmail.com 3 Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt; ahmedpharma8530@gmail.com (A.M.S.); abuh20050@yahoo.com (H.M.H.) 4 Laboratory of Soil Biology, University of Neuchatel, 2000 Neuchatel, Switzerland; lassaad.belbahri@unine.ch 5 Departement of Forest Protection, Forest Research Institute, 05-090 S˛ ekocin Stary, Poland; T.Oszako@ibles.waw.pl 6 Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt 7 Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt * Correspondence: usama.ramadan@mu.edu.eg; Tel.: +2-86-2347759 † Equal contribution. Abstract: The acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) caused severe panic all over the world. The coronavirus (COVID-19) outbreak has already brought massive human suffering and major economic disruption and unfortunately, there is no specific treatment for COVID-19 so far. Herbal medicines and purified natural products can provide a rich resource for novel antiviral drugs. Therefore, in this review, we focused on the sterols and triterpenes as potential candidates derived from natural sources with well-reported in vitro efficacy against numerous types of viruses. Moreover, we compiled from these reviewed compounds a library of 162 sterols and triterpenes that was subjected to a computer-aided virtual screening against the active sites of the recently reported SARS-CoV-2 protein targets. Interestingly, the results suggested some compounds as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics. Keywords: sterols; triterpenes; antiviral potential; SARS-CoV-2 1. Introduction Steroids and triterpenes are considered common natural product classes that are widespread in different marine and terrestrial natural sources (e.g., plants, animals, and microorganisms) [1–3]. Additionally, they comprise many sub-classes with enormous chemical diversity. These two classes of compounds have been provided several successful drugs for various ailments since the discovery of digoxin in 1785, like cortisol, fusidic acid, carbenoxolone, and β-Aescin [4]. These compounds possess a myriad of biological activities, digoxin used in the treatment of heart failure and atrial fibrillation [5], fusidic acid used as topical antibiotics [6]. Carbenoxolone enhances peripheral insulin sensitiv- ity [7] and treatment of gastric ulcer [8] and β-Aescin used in the treatment of human hepatocellular carcinoma SMMC-7721 cells [9]. Steroids and triterpenes possess various potential antiviral properties such as anti-Herpes simplex virus activity [10], anti-hepatitis B activity [11], anti-HIV1 and 2, AIDS, and hepatitis C virus activities [12]. Steroids class consists of 25 chemical subclasses with about 11,825 compounds that have been previously reported [13] (Figure 1A) While, triterpenoids class of compounds consists of 47 chemical subclasses with about 18,864 chemical compounds that were previously, isolated, and identified from different natural sources as shown in (Figure 1B). Plants 2021, 10, 41. https://dx.doi.org/10.3390/plants10010041 https://www.mdpi.com/journal/plants