Author(s): Muchtaridi Muchtaridi, Adham Rizki Ananda, Fajri Raihan, Indah Permata Rendi, Cecep Suhandi, Driyanti Rahayu


DOI: 10.52711/0974-360X.2023.00500   

Address: Muchtaridi Muchtaridi*, Adham Rizki Ananda, Fajri Raihan, Indah Permata Rendi, Cecep Suhandi, Driyanti Rahayu
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
*Corresponding Author

Published In:   Volume - 16,      Issue - 6,     Year - 2023

COVID-19 is a disease caused by SARS-CoV-2 and since 2020 has become a pandemic by affecting at least millions of people with a mortality rate of over 4 million worldwide. COVID-19 has fourteen drug targets with main protease (Mpro) as the most potential enzyme for inhibition. There is a catalytic dyad in Mpro which is the main key to determine the inhibitory potential of a ligand in COVID-19. Currently, the drug for Mpro inhibition in COVID-19 has not been found. Many articles have been published discussing the interaction and inhibitory potential of drugs against Mpro in COVID-19, so it is necessary to draw a conclusion to select drug candidates with the best potency. PMC and ScienceDirect are two databases used for article screening. Research using molecular docking simulation of Mpro with Gibbs energy parameters and the interaction between the ligand and Mpro is the focus of this review. Compounds that achieve the docking parameters are carefully ranked. There are 28 articles with a total of 118 compounds that achieve the docking parameters ranked. The top three compounds were dihydroergotoxine (?G = -10.14kcal/mol), imatinib (?G = -10.12kcal/mol), and hyaluronic acid (?G = -13.54 kcal/mol) with the highest binding mode and inhibitory potential on catalytic dyads. These compounds need to be considered for further research.

Cite this article:
Muchtaridi Muchtaridi, Adham Rizki Ananda, Fajri Raihan, Indah Permata Rendi, Cecep Suhandi, Driyanti Rahayu. A Narrative Review: Molecular Docking Simulation of Antiviral Drugs as Anti-COVID-19 Candidates. Research Journal of Pharmacy and Technology 2023; 16(6):3031-7. doi: 10.52711/0974-360X.2023.00500

Muchtaridi Muchtaridi, Adham Rizki Ananda, Fajri Raihan, Indah Permata Rendi, Cecep Suhandi, Driyanti Rahayu. A Narrative Review: Molecular Docking Simulation of Antiviral Drugs as Anti-COVID-19 Candidates. Research Journal of Pharmacy and Technology 2023; 16(6):3031-7. doi: 10.52711/0974-360X.2023.00500   Available on:

1.    Rokade M, Khandagale P. Coronavirus Disease: A Review of a New Threat to Public Health. Asian J Pharm Res. 2020;10(3):241-244. doi:10.5958/2231-5691.2020.00042.8
2.    Organization WH. WHO Coronavirus (COVID-19) Dashboard. July 23, 2021. Accessed July 23, 2021.
3.    Ali AD. SARS-CoV-2 is Originated from Bat Corona Virus. Research J. Science and Tech. 2021; 13(1):31-32. doi: 10.5958/2349-2988.2021.00005.X
4.    Akshay G, Rutuja S, Shreya P, Prajakta K. SARS-Cov-2 The Beta Genome Coronavirus: A Brief Overview, Pathogenesis and Treatment. Asian J. Res. Pharm. Sci. 2020; 10(4):299-310. doi: 10.5958/2231-5659.2020.00052.1
5.    Subhashis D, Jaya S. Coronavirus disease (COVID-19): A global threat. AJPTech. 2022; 12(1):63-9. doi: 10.52711/2231-5713.2022.00011
6.    Archana BC, Pavan SJ, Satish S. COVID 19: Outbreak, Structure and Current therapeutic strategies. Asian J. Pharm. Tech. 2021; 11(1):76-83. doi: 10.5958/2231-5713.2021.00013.1
7.    Ouassou H, Kharchoufa L, Bouhrim M, et al. The Pathogenesis of Coronavirus Disease 2019 (COVID-19): Evaluation and Prevention. J Immun Res. 2020;2020:1357983-1357983. doi:10.1155/2020/1357983
8.    Balai MK. UK Variant COVID-19. Asian J Nurs Edu Res. 2021;11(4):601-4. doi:10.52711/2349-2996.2021.00140
9.    Naresh BV. A Review of the 2019 Novel Coronavirus (COVID-19) Pandemic. Asian J Pharm Res. 2020;10(3):233-238. doi:10.5958/2231-5691.2020.00040.4
10.    Ayoub A, Fatima N, Kaushik V. Pulmonary Aerosolized Formulation or Nasal Drops containing Recombinant Human Angiotensin converting Enzyme 2 (rhACE2) as a Potential Therapy against COVID-19. Res J Pharm Tech. 2021;14(6):3433-6. doi:10.52711/0974-360X.2021.00597
11.    Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung SH. An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. J Med Chem. Jul 28 2016;59(14):6595-628. doi:10.1021/acs.jmedchem.5b01461
12.    Rithiga BS, Shanmugasundaram S. Virtual Screening of Pentahydroxyflavone – A Potent COVID-19 Major Protease Inhibitor. Asian J Res PharmSci. 2021;11(1):7-14. doi:10.5958/2231-5659.2021.00002.3
13.    Naveen Y, Ganta S. Prediction of COVID-19 severity associated with Pneumonia by chest CT scan and Serological results. AJPTech. 2021; 11(3):198-2. doi: 10.52711/2231-5713.2021.00032
14.    Wankhede DK. COVID-19- Problem faced by Indians during Lockdown Asian J Nurs Edu Res. 2020;10(4):501-504. doi:10.5958/2349-2996.2020.00108.1
15.    Gadge SS. Antiviral and Immunity-modulating Natural Herbs in the Prevention of COVID-19. Res J Pharmacog Phytochem. 2021;13(2):81-4. doi:10.52711/0975-4385.2021.00014
16.    Auwaerter PG, Casadevall A. Is the Coronavirus Treatable? John Hopkins Medicine. July 23, 2021. Accessed July 23, 2021.
17.    Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. May 2020;10(5):766-788. doi:10.1016/j.apsb.2020.02.008
18.    Otuokere IE, Amaku FJ, Alisa CO. In Silico Geometry Optimization, Excited – State Properties of (2E)-N-Hydroxy-3-[3-(Phenylsulfamoyl) Phenyl] prop-2-Enamide (Belinostat) and its Molecular Docking Studies with Ebola Virus Glycoprotein. Asian J Pharm Res. 2015;5(5):131-137. doi:10.5958/2231-5691.2015.00020.9
19.    Hemalatha K, Selvin J, Girija K. Synthesis, In silico Molecular Docking Study and Anti-bacterial Evaluation of some Novel 4-Anilino Quinazolines. Asian J Pharm Res. 2018;8(8):125-132.
20.    A. Anto Arockia Raj, J. Vinnarasi. Natural Potential Inhibitors for Covid 19 – An Insilico Approach. Research Journal of Pharmacy and Technology. 2021; 14(9):4913-9. doi: 10.52711/0974-360X.2021.00854
21.    Safiya ST, Umamaheswari S, Sivakumar M, Umar KS. De Novo In-silico Pharmacological Analysis of Herbal Phytoconstituents for COVID-19 Treatment. Research Journal of Pharmacy and Technology. 2022; 15(1):257-2. doi: 10.52711/0974-360X.2022.00042
22.    Prachi P, Bhaskar S, Sayandeep KD, R. Chandramouli Reddy, Shrilaxmi Bagali, Raghavendra V. Kulkarni, Aravind V. Patil, Mallanagoud S. Biradar, Kusal K. Das. Molecular Docking Identifies Novel Phytochemical Inhibitors Against SARS-COV-2 for Covid-19 Therapy. Research Journal of Pharmacy and Technology. 2022; 15(2):555-8. doi: 10.52711/0974-360X.2022.00090
23.    Sindhu TJ, Arathi KN, Akhilesh KJ, Anju J, Binsiya KP, Blessy T, Elizabeth W. Antiviral screening of Clerodol derivatives as COV 2 main protease inhibitor in Novel Corona Virus Disease: In silico approaches. Asian J. Pharm. Tech. 2020; 10(2):60-64. doi: 10.5958/2231-5713.2020.00012.4
24.    S. Bhavanisha Rithiga, S. Shanmugasundaram. Virtual Screening of Pentahydroxyflavone – A Potent COVID-19 Major Protease Inhibitor. Asian J. Res. Pharm. Sci.2021;11(1):7-14. doi: 10.5958/2231-5659.2021.00002.3
25.    Eleftheriou P, Amanatidou D, Petrou A, Geronikaki A. In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus. Molecules. 2020;25(11)doi:10.3390/molecules25112529
26.    Jain R, Mujwar S. Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19. Struc Chem. 2020/12/01 2020;31(6):2487-2499. doi:10.1007/s11224-020-01605-w
27.    Kumar D, Kumari K, Vishvakarma VK, et al. Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation. J Biomol Struct Dynamics. 2020:1-15. doi:10.1080/07391102.2020.1779131
28.    Tariq A, Mateen RM, Afzal MS, Saleem M. Paromomycin: A potential dual targeted drug effectively inhibits both spike (S1) and main protease of COVID-19. Inter J Infec Dis. 2020/09/01/ 2020;98:166-175. doi:
29.    Pinzi L, Tinivella A, Caporuscio F, Rastelli G. Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease. Front Pharmacol. 2021;12:636989. doi:10.3389/fphar.2021.636989
30.    Ibrahim MAA, Abdelrahman AHM, Hegazy M-EF. In-silico drug repurposing and molecular dynamics puzzled out potential SARS-CoV-2 main protease inhibitors. J Biomol Struct Dynamics. 2020:1-12. doi:10.1080/07391102.2020.1791958
31.    Ahmed MZ, Zia Q, Haque A, et al. Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents. J Inf Pub Health. 2021/05/01/ 2021;14(5):611-619. doi:
32.    Elmezayen AD, Al-Obaidi A, Şahin AT, Yelekçi K. Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. J Biomol Struct Dynamics. 2021/05/24 2021;39(8):2980-2992. doi:10.1080/07391102.2020.1758791
33.    Peele KA, Potla Durthi C, Srihansa T, et al. Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study. Info Med Unlocked. 2020/01/01/ 2020;19:100345. doi:
34.    Shamsi A, Mohammad T, Anwar S, et al. Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy. Biosci Rep. 2020;40(6)doi:10.1042/BSR20201256
35.    Gumber K, Pomila. FDA recommended potent drugs against COVID-19: Insight through molecular docking. Materials Today Proceed. 2021;45:3328-3335. doi:10.1016/j.matpr.2020.12.649
36.    Hasan M, Parvez MSA, Azim KF, et al. Main protease inhibitors and drug surface hotspots for the treatment of COVID-19: A drug repurposing and molecular docking approach. Biomed Pharmaco. 2021/08/01/ 2021;140:111742. doi:
37.    Meyer-Almes F-J. Repurposing approved drugs as potential inhibitors of 3CL-protease of SARS-CoV-2: Virtual screening and structure based drug design. Comput Biol Chem. 2020;88:107351-107351. doi:10.1016/j.compbiolchem.2020.107351
38.    Sajid Jamal QM, Alharbi AH. Identification of doxorubicin as a potential therapeutic against SARS-CoV-2 (COVID-19) protease: a molecular docking and dynamics simulation studies. J Biomol Struct Dynamics. Apr 7 2021:1-15. doi:10.1080/07391102.2021.1905551
39.    Khater I, Nassar A. In silico molecular docking analysis for repurposing approved antiviral drugs against SARS-CoV-2 main protease. Biochem Biophys Rep. 2021/09/01/ 2021;27:101032. doi:
40.    Molavi Z, Razi S, Mirmotalebisohi SA, et al. Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach. Biomed Pharmaco. 2021/06/01/ 2021;138:111544. doi:
41.    Pathak Y, Mishra A, Choudhir G, Kumar A, Tripathi V. Rifampicin and Letermovir as potential repurposed drug candidate for COVID-19 treatment: insights from an in-silico study. Pharmacol Rep. 2021;73(3):926-938. doi:10.1007/s43440-021-00228-0
42.    Nejat R, Sadr AS. Are losartan and imatinib effective against SARS-CoV2 pathogenesis? A pathophysiologic-based in silico study. In Silico Pharmacol. 2020;9(1):1-1. doi:10.1007/s40203-020-00058-7
43.    Bhowmik D, Sharma RD, Prakash A, Kumar D. “Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CLpro and PLpro". J Mol Struc. 2021/06/05/ 2021;1233:130094. doi:
44.    Abosheasha MA, El-Gowily AH. Superiority of cilostazol among antiplatelet FDA-approved drugs against COVID 19 Mpro and spike protein: Drug repurposing approach. Drug Dev Res. 2021/04/01 2021;82(2):217-229. doi:
45.    Reiner Ž, Hatamipour M, Banach M, et al. Statins and the COVID-19 main protease: in silico evidence on direct interaction. Arch Med Sci. 2020;16(3):490-496. doi:10.5114/aoms.2020.94655
46.    Ghosh R, Chakraborty A, Biswas A, Chowdhuri S. Potential therapeutic use of corticosteroids as SARS CoV-2 main protease inhibitors: a computational study. J Biomol Struct Dynamics. 2020:1-14. doi:10.1080/07391102.2020.1835728
47.    Deshpande RR, Tiwari AP, Nyayanit N, Modak M. In silico molecular docking analysis for repurposing therapeutics against multiple proteins from SARS-CoV-2. Europ J Pharmacol. 2020;886:173430-173430. doi:10.1016/j.ejphar.2020.173430
48.    Abo Elmaaty A, Hamed MIA, Ismail MI, et al. Computational Insights on the Potential of Some NSAIDs for Treating COVID-19: Priority Set and Lead Optimization. Molecules. 2021;26(12)doi:10.3390/molecules26123772
49.    Mishra D, Maurya RR, Kumar K, et al. Structurally modified compounds of hydroxychloroquine, remdesivir and tetrahydrocannabinol against main protease of SARS-CoV-2, a possible hope for COVID-19: Docking and molecular dynamics simulation studies. J Mol Liq. Aug 1 2021;335:116185. doi:10.1016/j.molliq.2021.116185
50.    Elzupir AO. Caffeine and caffeine-containing pharmaceuticals as promising inhibitors for 3-chymotrypsin-like protease of SARS-CoV-2. J Biomol Struct Dynamics. 2020:1-8. doi:10.1080/07391102.2020.1835732
51.    Azam F, Taban IM, Eid EEM, et al. An in-silico analysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α. J Biomol Struc Dynamics. 2020:1-14. doi:10.1080/07391102.2020.1841028
52.    Elzupir AO. Inhibition of SARS-CoV-2 main protease 3CLpro by means of α-ketoamide and pyridone-containing pharmaceuticals using in silico molecular docking. J Mol Struc. 2020/12/15/ 2020;1222:128878. doi:
53.    Baby K, Maity S, Mehta CH, Suresh A, Nayak UY, Nayak Y. Targeting SARS-CoV-2 Main Protease: A Computational Drug Repurposing Study. Arch Med Res. 2021;52(1):38-47. doi:10.1016/j.arcmed.2020.09.013
54.    Arathi STJ, Akhilesh KN, Anju KJ, Binsiya J, Blessy KP, Elizabeth Wilson T. Antiviral screening of Clerodol derivatives as COV 2 main protease inhibitor in Novel Corona Virus Disease: In silico approaches. Asian J Pharm Tech. 2020;10(2):60-64. doi:10.5958/2231-5713.2020.00012.4
55.    Satpute UM, Rohane SH. Efficiency of AUTODOCK: Insilico study of Pharmaceutical Drug Molecules. Asian J Research Chem. 2021;14(1):92-96. doi:10.5958/0974-4150.2021.00016.X

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available