Main Article Content



The CADD includes the combined use of modern computational and experimental techniques which provide structural information about the biologically active molecules. These molecules are involved in disease process and in modulating disease process. The processes of CADD methods are dependent on Bioinformatics tools, applications and database.

The present Review article highlights how the modern computational and experimental techniques that have been developed in recent years can be used together to provide structural information about the biologically active molecules that are involved in disease process and in modulating disease process in Special focus to Drug designing for COVID 19 by virtual Screening.

Out Put of the article: The present article may be one tool for new drug development against corona Virus.

Bioinformatics, molecular biology, combinatorial chemistry, isolaton, nomenclature

Article Details

How to Cite
RAY, B., PANIGRAHI, A. K., DUTTA, S., & GOCHAYAT, M. (2021). COMPUTER AIDED DRUG DESIGN: TOOLS TO DEVELOP DRUG FOR COVID 19. Asian Journal of Advances in Medical Science, 3(4), 127-146. Retrieved from
Review Article


Review of Computer Aided Drug Design in Drug Delivery; 2017.

Lengauer. Bioinformatics. From Genomes to Drugs. Wiley- VCH, Weinheim, Germany; 2002.

Hou T, Xu X. Recent development and Application of Virtual Screening in Drug Discovery: An Overview. Current Pharmaceutical Design. 2004;10:1011-1033.

Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nature Reviews in Drug Discovery. 2004;3:935-949.

DiMasi JA. Grabowski H G. The cost of biopharmaceutical R&D: is biotech different? Managerial and Decision Economics. 2007;28:469-479.

Review Paper of Computer Aided Drug Designing; 2020.

Halloway MK. A prior Prediction of ligand affinity by energy minimization. Perspectives in Drug Discovery and Designing. 1998;9(11):63-84.

Bakheet TM, Doig AJ. Properties and identifification of human protein drug targets. Bioinformatics. 2009;25:451-457.

Richards WG. Computer-Aided Drug Design. Pure and Applied Chemistry. 1994;6(68):1589-1596.

Walsh C. Where will new antibiotics come from? Nat Rev Micro. 2003;1:65–70.

Clark DE. What has computer-aided molecular design ever done for drug discovery? Expert Opinion. Drug Discov. 2006;1:103–110. DOI: 10.1517/17460441.1.2.103.

Huang SY, Zou X. Advances and challenges in protein-ligand docking. Int. J. Mol. Sci. 2010;11:3016–3034.

Taylor RD, Jewsbury PJ, Essex JW. A review of protein-small molecule docking methods. J. Comput. Aided Mol. Des. 2002;16:151–166.

Huang SY, Zou X. Advances and challenges in protein-ligand docking. Int. J. Mol. Sci. 2010;11:3016–3034

Jain AN. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J. Med. Chem. 2003;46:499-511.

Akoka J, Comyn-Wattiau I, Laoufi N. Research on big data—A systematic mapping study. Comput. Stand. Interfaces. 2017;54:105–115.

Feher M. Consensus scoring for protein-ligand interactions. Drug. Discov. Today. 2006;11:421-428.

Shimada J, Ishchenko AV, Shakhnovich EI. Analysis of knowledge-based protein-ligand potentials using a self-consistent method. Protein. Sci. 2000;9:765-775.

Kuritzkes D, Kar S, Kirkpatrick P. Maraviroc. Nat. Rev. Drug Discov. 2008;7:15.

Bishop CM. Model-based machine learning. Philos Trans. A Math. Phys. Eng. Sci. 2013;371:20120222.

Pant S, Singh M, Ravichandiran V, Murty USN, et al. Peptide-like and small-molecule inhibitors against Covid-19.J Biomol Struct Dyn. 2020;1-10.

AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–954.

Lee N, Hui D, Wu A, et al. A major out break of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348:1986-94. DOI: 10.1056/NEJMoa030685

Sen GC. Viruses and interferons. Annu Rev Microbiol. 2001;55:255-281.

Tilg H. New insights into the mechanisms of interferon Alfa: An immunoregulator and anti-inflammatory cytokine. Gastroenterology. 1997;112:1017-1021.

Morgenstern B, Michaelis M, Baer PC, Doerr HW, Cinatt J. Ribavirin and interferon-beta synergistically inhibits SARS-associated corona virus replication in animal and human cell lines. Biochem Biophys Res Commun. 2005;326:905-8. DOI: 10.1016/j.bbrc.2004.11.128

Wang WK, Chen SY, Liu IJ, Kao CL, Chen HL, Chiang BL, et al. Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome. Clin Infect Dis. 2004;39:1071-5. DOI: 10.1086/423808

Khalid M, Al Rabiah F, Khan B, Al Mobeireek A, Butt TS, Al Mutairy E. Ribavirin and interferon-α2b as primary and preventive treatment for Middle East respiratory sybdroms corona virus: a preliminary report of two cases Antivir Ther. 2005;20:87-91. DOI: 10.3851/IMP2792

Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life sci. 2020;248:117477. DOI: 10.1016/j.lfs.2020.117477

Dong L, Hu S, Gao J. Discovering drugs to trat coronavirus disease 2019. (COVID-19). Drug Discov Ther. 2020;14:58-60. DOI: 10.5582/ddt.2020.01012

Elfiky AA. Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking studt. Life Sci. 2020;253:117592. DOI: 10.1016/j.lfs.2020.117592

Cameron CE, Castro C. The mechanism of action of ribavirin: lethal mutagenesis of RNA virus genomes mediated by the viral RNA-dependent RNA polymerase. Curr Opin Infect Dis. 2001;14:757-64.

Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong [online]. N Engl J Med. Available: (posted 2003 Mar 31; accessed 2003 Apr- 15).

Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report.

Jin Z, Smith LK, Rajwanshi VK, Kim B, Deval J. The ambiguous base-pairing and high substrate efficiency of T-705 (favipiravir) ribofuranosyl 5’-triphosphate towards influenza A virus polymerase. PloS One. 2013;8.

Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463. DOI: 10.2183/pjab.93.027 Baranovich et. al.; 2013.

Baranovich T, Wong SS, Armstrong J. 705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol. 2013;87:3741-3751.

Rhyman L, Tursun M, Abdallah HH, Choong YS, Parlak C, Kharkar P, Ramasami P. Theoretical investigation of the derivatives of favipiravir (T-705) as potential drugs for Ebola virus. Physical Sciences Reviews. 2018;3(9).

Zhong H, Wang Y, Zhang ZL, Liu YX, Le KJ, Cui M, Yu YT, Gu ZC, Gao Y, Lin HW. Efficacy and safety of current therapeutic options for COVID-19- lessons to be learnt from SARS and MERS epidemeic: A systematic review and meta-analysis. Pharmacol. Res. 2020;157:104872. DOI : 10.1016/j.phrs.2020.104872

Dagens A, Sigfrid L, Cae E, et al. Scope, quality, and inclusivity of clinical guidelines produced early in the COVID-19 pandemic: rapid review. BMJ. 2020;369m1936

Nukoolkrn V, Lee VS, Malaisree M, Aruksakulwong O, Hannongbua S. Molecular dynamic stimulations analysis of ritonavir and lopinavir as SARS-CoV 3CL(pro) inhibitors. J Theor Biol. 2008;256:861-867.

Chen F, Chan KH, Jiang Y, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004;31:69-75.

de Wilde AH, Jochmans D, Posthuma CC, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East Respiratory Syndrome corona virus replication in cell culture. Antimicrob Agents Chemother. 2014;58:4875-4884.

Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11:222.

Zhang L, Lin D, Sun X, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors. Science; 2020. DOI: 10.1126/science.abb3405

Anand K, Ziebuhr J, Wadhwani P, et al. Corona virus main proteinase (3CL pro) structure: basis for design of anti-SARS drugs. Science. 2003;300(5626):1763-7. DOI: 10.1126/science

Vastag B. Old drugs for a new bug. JAMA. 2003;290(13):1695-96.

Choy KT, Yin-Lam Wong A, Kaewpreedee P, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020:104786. DOI: 10.1016/j.antiviral.2020.104786

Takashiro E, Hayakawa I, Nitta T, Kasuya A, Miyamoto S, Ozawa Y, Yagi R, Yamamoto I, Shibayama T, Nakagawa A, Yabe Y. Structure–activity relationship of HIV-1 protease inhibitors containing α-hydroxy-β-amino acids. Detailed study of P1 site. Bioorganic & medicinal chemistry. 1999;7(9):2063-72.

Computed by LexiChem 2.6.6 (PubChem release 2019.06.18).

Malin JJ, Suarez I, Priesner V, Fatkenheuer G, Rybniker J. Remdesivir against COVID-19 and Other Viral Diseases. Clin Microbiol Rev. 2020;34(1). Pii: 34/1/e00162-20. DOI: 10.1128/CMR.00162-20.

Humeniuk R, Mathias A, Kirby BJ, Lutz JD, Cao H, Osinusi A, Babusis D, Porter D, Wei X, Ling J, Reddy YS, German P. Pharmacokinetic, Pharmacodynamics, and Drug-Interaction Profile of Remdesivir, a SARS-CoV-2 Replication Inhibitor. Clinical pharmacokinetics; 2021.

Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Gotte M. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020;295(20):6785-6797. DOI: 10.1074/jbc.RA120.013679. Epub 2020 Apr 13.l

De Clercq E. Strategies in the design of antiviral drugs. Nat Rev Drug Discov. 2002;1(1):13–25. DOI: 10.1038/nrd703. Mehellou Y, Balzarini J, McGuigan C. Aryloxy phosphoramidate triesters: a technology for delivering monophosphorylated nucleosides and sugars into cells. Chem Med Chem. 2009;4(11):1779–1791. DOI: 10.1002/cmdc.200900289

Seley-Radtke KL, Yates MK. The evolution of nucleoside analogue antivirals: a review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold. Antiviral Res. 2018; 154:66–86. DOI: 10.1016/j.antiviral.2018.04.004

Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):1–4. DOI: 10.1038/s41467-019-13940-6

WHO model list of essential medicines. Accessed March 29,2011.

Elfiky AA. Ribavirin. Remdesivir. Sofosbuvir. Galidesivir. And Tenofovir against SARS-CoV -2 RdRp: A molecular docking study. Life Sci. 2020;253:117592.

Chien M, AndersonTK, Jockusch S, et al. Nucleotide analogues as inhibitors of SARS-CoV-2 Polymerase, a Key Drug Target for COVID-19. J Proteomase Res. 2020;19:4690-7.

Zandi K, Amblard F, Musall K, et al. Repurposing nucleoside analogs for human corona viruses. Antimicrob Agents Chemother. 2020;65. DOI: 10.1128/AAC.01652-20.

Muralidharan N, Sakthivel R, Velmurugan D, Gromiha MM. Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 protease against COVID-19. J Biomol Struct Dyn. 2020;1-6. DOI: 10.1080/07391102.2020.1752802.

Anderson PL, Kiser JJ, Gardner EM, Rower JE, Meditz A, Grant RM. Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection. J Antimicrob Chemother. 2011;66(2):240‐50.

Chien M, Anderson TK, Jockusch S, et al. Nucleotide analogues as inhibitors of SARS‐CoV‐2 polymerase, a key drug target for COVID‐19. J Proteome Res. 2020;19(11):4690‐4697.

Elfiky AA. Ribavirin, remdesivir , sofosbuvir, galidesivir, and tenofovir against SARS‐CoV‐2 RNA dependent RNA polymerase (RdRp): a molecular docking study. Life Sci. 2020;253:117592.

Clososki GC, Soldi RA, Silva RM da, et al. Tenofovir Disoproxil Fumarate: New chemical developments and encouraging in vitro biological results for SARS-CoV-2. J Braz Chem Soc. 2020;31:1552-6.

Park S-J, Yu K-M, Kim T-I, et al. Antiviral Efficacies of FDA- approved drugs against SARS-CoV-2 infection in Ferrets. mBio. 2020;11. DOI:10.1128/mBio.01114-20.

Del Amo J, Polo R, Moreno S, et al. Incidence and severity of COVID‐19 in HIV‐positive persons receiving antiretroviral therapy: a cohort study. Ann Intern Med. 2020;173(7): 536‐541.

Elfiky A. A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020;253:117592.

Clososki GC, Soldi RA, RMd Silva, et al. Tenofovir disoproxil fumarate: new chemical developments and encouraging in vitro biological results for SARS‐CoV‐2. J Braz Chem Soc. 2020;31(8):1552‐1556.

Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. Collier AC, Coombs RW, Schoenfeld DA, Bassett RL, Timpone J, Baruch A, Jones M, Facey K, Whitacre C, McAuliffe VJ, Friedman HM, Merigan TC, Reichman RC, Hooper C, Corey LN Engl J Med. 1996;16:1011-1017. MED:8598838

Schapiro JM, et al. The effect of high-dose saquinavir on viral load and CD4+ T-cell counts in HIV-infected patients. Ann Intern Med. 1996;124(12):1039–1050.

De Clercq E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009;33(4):307-20. DOI: 10.1016/j.ijantimicag.2008.10.010. Epub 2008 Dec 23.

DA Approved Drug Products: Invirase (saquinavir mesylate) oral tablets. LiverTox LICENSE Saquinavir

South Asian Journal of Experimental Biology, Vol 2, No 3 (2012). QSAR of Saquinavir Analogues (Peptidomimetics) as Potent HIV‐Protease Inhibitors. Vandana Saini, Ajit Kumar. Available:

Chikanza IC. Mechanisms of corticosteroid resistance in rheumatoid arthritis: a putative role for the corticosteroid receptor beta isoform. Ann N Y Acad Sci. 2002;966:39– 48. DOI: 10.1111/j.1749-6632.2002.tb04200.x.

Grzanka A, Misiołek M, Golusiński W, Jarząb J. Molecular mechanisms of glucocorticoids action: implications for treatment of rhinosinusitis and nasal polyposis. Eur Arch Otorhinolaryngol. 2011;268:247–253. DOI: 10.1007/s00405-010-1330-z.

FDA Approved Drug Products: Maxitrol Neomycin, Polymyxin B, and Dexamethasone Ophthalmic Ointment.

FDA Approved Drug Products: Tobradex Tobramycin and Dexamethasone Ophthlamic Suspension. Available: DICTIONARY.COM UNABRIDGED BASED ON THE RANDOM HOUSE UNABRIDGED DICTIONARY, © RANDOM HOUSE, INC. 2021

Devaux CA, Rolain JM, 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;55:19–20. DOI: 10.1016/j.ijantimicag.2020.105938.

Sahraei Z, Shabani M, Shokouhi S, Saffaei A. Aminoquinolines against coronavirus disease 2019 (COVID-19): Chloroquine or hydroxychloroquine. Int J Antimicrob Agents. 2020;55:1– 3. DOI: 10.1016/j.ijantimicag.2020.105945.

Gevers S, Kwa MSG, Wijnans E, van Nieuwkoop C. Safety considerations for chloroquine and hydroxychloroquine in the treatment of COVID-19. Clin Microbiol Infect Published online. 2020:4539–47. DOI: 10.1016/j.cmi.2020.05.006.

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. Available:10.1016/j.ijantimicag.2020.105949Clinical trial favouring use of HCQ with azithromycin in COVID-19 patients.

Skipper CP, Pastick KA, Engen NW, Bangdiwala AS, Abassi M, Lofgren SM, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19. Ann Intern Med. 2020:M20–4207. DOI: 10.7326/M20-4207 Accessed 22 July 2020.

Muraleedharan KM, Avery MA. In Comprehensive Medicinal Chemistry II. Therapeutic Areas II: Cancer, Infectious Diseases, Inflammation, Immunology and Dermatology; Taylor JB, Triggle DJ, Eds.