American Journal of Pharmacological Sciences
ISSN (Print): 2327-6711 ISSN (Online): 2327-672X Website: Editor-in-chief: Srinivas NAMMI
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American Journal of Pharmacological Sciences. 2020, 8(1), 9-13
DOI: 10.12691/ajps-8-1-3
Open AccessArticle

Developing Potential Drugs for COVID-19 Using Ligand Based Virtual Screening

Kagia Richard1,

1Department of Pharmacology & Pharmacognosy, Kabarak University, Nakuru, Kenya

Pub. Date: May 11, 2020

Cite this paper:
Kagia Richard. Developing Potential Drugs for COVID-19 Using Ligand Based Virtual Screening. American Journal of Pharmacological Sciences. 2020; 8(1):9-13. doi: 10.12691/ajps-8-1-3


Background and purpose: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-CoV2) is a highly contagious disease that has infected more than 2.4 million patients and led to more than 160, 000 deaths in less than five months. Chloroquine is very effective in management of COVID-19. Compounds similar to chloroquine may have the same biological activity and thus inhibit SARS-CoV2. Methods: SwissSimilarity tool was used to identify similar compounds to chloroquine in the ZINC database. Compounds which were more similar than hydroxychloroquine were selected and used to test molecular docking with quinone reductase 2 (a target for chloroquine). Pharmacokinetic and toxicity profiles of selected compounds were assessed using SwissADME and Protox Server respectively. Results: There were 49 drug-like compounds in the ZINC database having a higher similarity index to chloroquine compared to hydroxychloroquine. 17 of these had a better binding potential to quinone reductase 2 compared to chloroquine while two had similar binding potential to chloroquine and three had similar binding potential to hydroxychloroquine. Out of these 22 compounds, 18 had a higher predicted LD50 compared to chloroquine but lower when compared to hydroxychloroquine. Conclusion: Eighteen drug-like compounds in the ZINC database bind with high affinity to quinone reductase 2, are less toxic but similar to chloroquine. Therefore, they may have activity against SARS-CoV2. However, in vivo or in vitro study should be done since this is an in silico study.

COVID-19 SARS-CoV2 chloroquine quinone reductase ZINC database ligand-based virtual screening

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[1]  Hageman JR. The Coronavirus Disease 2019 (COVID-19). Pediatr Ann 2020; 49: e99-100.
[2]  Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020.
[3]  Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020:727-33.
[4]  Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet 2020; 395: 470-3.
[5]  Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020; 3099: 19-20.
[6]  Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020; 14: 72-3.
[7]  Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res 2020; 177: 104762.
[8]  Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020: 3-7.
[9]  Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020: 105949.
[10]  Luzzi GA, Peto TEA. Adverse Effects of Antimalarials: An Update. Drug Saf 1993; 8: 295-311.
[11]  Thomé R, Lopes SCP, Costa FTM, Verinaud L. Chloroquine: Modes of action of an undervalued drug. Immunol Lett 2013; 153: 50-7.
[12]  Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 1-10.
[13]  Devaux CA, Rolain J-M, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 2020: 105938.
[14]  Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis 2006; 6: 67-9.
[15]  Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020; 46: 586-90.
[16]  Shoichet BK. Virtual screening of chemical libraries. Nature 2004; 432: 862-5.
[17]  Patrick Walters W, Stahl MT, Murcko MA. Virtual screening - An overview. Drug Discov Today 1998; 3: 160-78.
[18]  Zoete V, Daina A, Bovigny C, Michielin O. Swiss Similarity: A Web Tool for Low to Ultra High Throughput Ligand-Based Virtual Screening. J Chem Inf Model 2016; 56: 1399-404.
[19]  Irwin JJ, Shoichet BK. ZINC - A free database of commercially available compounds for virtual screening. J Chem Inf Model 2005; 45: 177-82.
[20]  Sterling T, Irwin JJ. ZINC 15 - Ligand Discovery for Everyone. J Chem Inf Model 2015; 55: 2324-37.
[21]  Hanwell MD, Curtis DE, Lonie DC, Vandermeerschd T, Zurek E, Hutchison GR. Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 2012; 4.
[22]  Yang Z, Lasker K, Schneidman-Duhovny D, Webb B, Huang CC, Pettersen EF, et al. UCSF Chimera, MODELLER, and IMP: An integrated modeling system. J Struct Biol 2012; 179: 269-78.
[23]  Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7: 1-13.
[24]  Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 2018; 46: W257-63.
[25]  Lipinski CA. Lead- and drug-like compounds: The rule-of-five revolution. Drug Discov Today Technol 2004; 1: 337-41.
[26]  Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 2002; 45: 2615-23.
[27]  Leung KKK, Shilton BH. Chloroquine binding reveals flavin redox switch function of quinone reductase 2. J Biol Chem 2013; 288: 11242-51.
[28]  Faber MS, Jetter A, Fuhr U. Assessment of CYP1A2 activity in clinical practice: Why, how, and when? Basic Clin Pharmacol Toxicol 2005; 97: 125-34.
[29]  Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005; 5: 6-13.
[30]  Kenworthy KE, Bloomer JC, Clarke SE, Houston JB. CYP3A4 drug interactions: Correlation of 10 in vitro probe substrates. Br J Clin Pharmacol 1999; 48: 716-27.
[31]  Wedlund PJ. The CYP2C19 enzyme polymorphism. Pharmacology 2000; 61: 174-83.
[32]  Rettie AE, Jones JP. CLINICAL AND TOXICOLOGICAL RELEVANCE OF CYP2C9: Drug-Drug Interactions and Pharmacogenetics. Annu Rev Pharmacol Toxicol 2005; 45: 477-94.
[33]  Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis 2020.
[34]  Wang T, Du Z, Zhu F, Cao Z, An Y, Gao Y, et al. Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet 2020; 395: e52.