1958 Current Topics in Medicinal Chemistry, 2020, Vol. 20, No. 22 Abouleish et al. PERSPECTIVE IN MEDICINAL CHEMISTRY Importance of Environmental Factors on Production of Computationally- Defined Natural Molecules against COVID-19 Pandemic Mohamed Abouleish 1 , Ali El-Keblawy 2,* , Kareem A. Mosa 2,3 and Sameh S.M. Soliman 4 1 Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, P.O. Box 26666, United Arab Emirates; 2 Department of Applied Biology, College of Sciences, Uni- versity of Sharjah, Sharjah, P.O.Box 27272, United Arab Emirates; 3 Department of Biotechnology, Faculty of Agricul- ture, Al-Azhar University, Cairo, Egypt; 4 College of Pharmacy, University of Sharjah, Sharjah, P.O. Box 27272, United Arab Emirates Dear Editor, The outbreak caused by the novel Coronavirus (SARS-CoV-2) and designated COVID-19 by the World Health Organiza- tion (WHO), spread aggressively across the continents [1]. COVID-19 resulted in 6.93 million infected cases and over 401,000 deaths around the world as of June 09, 2020. The emergence of such pandemic infections poses serious threats to the global public health and world economy. Currently, there are no safe and effective drugs available for SARS-CoV-2, and the devel- opment of new antiviral drug is a time-consuming process, while the COVID-19 pandemic requires a quick response. There is an urgent need for defining a safe and guaranteed source of medicines including in particular medicinal plants that can fight SARS-CoV-2, especially in poor and developing countries, where they rely on herbal medicines as a main source of medi- cines. Plants produce a diverse number of secondary metabolites to fight against several types of pathogens including viruses [2]. The antiviral activities of some of these plant compounds make them possible candidates to fight against SARS-CoV-2. Computational modeling helped in proposing several plant compounds as potential candidates to inhibit SARS-CoV-2 by targeting enzymes that are necessary for viral pathogenesis. Molecular docking has been used to predict suitable active com- pounds that have high affinity to bind with the enzyme receptor (Angiotensin-converting enzyme 2, ACE2) to form a stable complex [3]. By using molecular docking, several compounds were suggested during the last few months as potential candi- dates to inhibit SARS-CoV-2. For example, Chen and Du [4] defined the potentials of five natural compounds for the preven- tion and treatment of SARS-CoV-2 infections; these are baicalin from Scutellaria baicalensis (Baikal skullcap), scutellarin from Erigeron breviscapus, hesperetin from Citrus aurantium (Bitter orange) and Citrus reticulate (mandarin orange), glycyr- rhizin from Glycyrrhiza radix (licorice), and nicotianamine from Glycine max (soybean). Similarly, ul Qamar et al. [5] virtually screened more than 32,297 antiviral phytochemicals and identified nine potential natural phytochemicals that can inhibit SARS- CoV-2 infection. These compounds are 5,7,3′,4′-tetrahydroxy-2’-(3,3-dimethylallyl) isoflavone from Psorothamnus arbores- cens, myricitrin from Myrica cerifera, methyl rosmarinate from Hyptis atrorubens, 3,5,7,3′,4′,5′-hexahydroxy flavanone-3-O- beta-D-glucopyranoside from Phaseolus vulgaris, (2S)-eriodictyol 7-O-(6″-O-galloyl) -beta-D-glucopyranoside from Phyllan- thus emblica, calceolarioside B from Fraxinus sieboldiana, myricetin 3-O-beta-D-glucopyranoside from Camellia sinensis, licoleafol from Glycyrrhiza uralensis, and amaranthin from Amaranthus tricolor. These phytochemicals showed higher binding affinity to ACE2 than other drugs used as control such as Nelfinavir, Prulifloxacin and Colistin [5]. Another study by Basu et al [6] reported five flavonoid and anthraquinone phytochemicals with potential inhibition activities of virus activation. These compounds are hesperidin from Valeriana jatamansi, emodin from Rheum emodi, anthraquinone from Cassia angustifolia, rhein from Cassia angustifolia, and chrysin from Oroxylum indicum [6]. Furthermore, Farshi et al. [7] reviewed over 110 arti- cles related to the effects of plant metabolites on different coronaviruses. Based on the IC 50 value, docking score, and binding energy, the authors were able to identify five natural compounds including curcumin from Curcuma longa (turmeric), hes- peridin and diosmin from citrus, apiin from Petroselinum crispum (parsely), and rutin from tea and apples, as promising inhibi- tors for the virus activation by targeting the host transmembrane protease serine 2 (TMPRSS2), which is a promising therapeu- tic target since it is critical for viral activation and invasion [7]. Inhibition of TMPRSS2 is an excellent target since it avoids possible development of drug resistance, a common viral feature [3]. Other computational analyses were conducted on plant compounds growing in the Middle East and North Africa have iden- tified different compounds with potential activities on coronavirus. For example, Aanouz et al. [8] assessed the activities of 67 antiviral compounds of natural origin derived from Moroccan plants. The results revealed three molecules including crocin from Crocus sativus, digitoxigenin from Nerium oleander, and β-eudesmol from Lauris nobilis that exhibited promising antivi- *Address correspondence to this author at the Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, P.O. Box 27272, United Arab Emirates; E-mail: akeblawy@sharjah.ac.ae 1873-4294/20 $65.00+.00 © 2020 Bentham Science Publishers