Study on SARS-CoV-2 inhibition of some potential drugs using molecular docking simulation

Cite this paper: Vietnam J. Chem., 2020, 58(5), 666-674 Article 
DOI: 10.1002/vjch.202000076 
666 Wiley Online Library © 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH 
Study on SARS-CoV-2 inhibition of some potential drugs using 
molecular docking simulation 
Tran Thi Ai My
1
, Le Trung Hieu
1
, Nguyen Thi Thanh Hai
1
, Huynh Thi Phuong Loan
1
, 
Thanh Q. Bui
1
, Bui Thi Phuong Thuy
2
, Phung Van Trung
3
, Bui Thi Bao Tram
4
, 
Nguyen Huyen Ngoc Tran
4
, Phan Tu Quy
5
, Duong Tuan Quang
6*
, Doan Thi Yen Oanh
7
, 
Pham Van Tat
8
, Duy Quang Dao
9,10
, Nguyen Thi Ai Nhung
1*
1
Department of Chemistry, University of Sciences, Hue University, 77 Nguyen Hue, Hue, 53000, Viet Nam 
2
Faculty of Fundamental Science, Van Lang University, 
45 Nguyen Khac Nhu, district 1, Ho Chi Minh, 70000, Viet Nam 
3
Center for Research and Technology Transfer, Vietnam Academy of Science and Technology, 
18 Hoang Quoc Viet, Cau Giay district, Hanoi 10000, Viet Nam 
4
Faculty of Medicine and Pharmacy, Van Lang University, Ho Chi Minh, 70000, Viet Nam 
5
Department of Natural Sciences and Technology, Tay Nguyen University, 
567 Le Duan Street, Buon Ma Thuot, 63000, Viet Nam 
6
University of Education, Hue University, 34 Le Loi, Hue, 53000, Viet Nam 
7
Publishing House for Science and Technology, Vietnam Academy of Science and Technology, 
18 Hoang Quoc Viet, Cau Giay, Hanoi 10000, Viet Nam 
8
Institute of Development and Applied Economics, Hoa Sen University, Ho Chi Minh, 70000, Viet Nam 
9
Institute of Research and Development, Duy Tan University, 
254 Nguyen Van Linh, Da Nang, 55000, Viet Nam 
10
Faculty of Environmental and Chemical Engineering, Duy Tan University, 
254 Nguyen Van Linh, Da Nang, 55000, Viet Nam 
Received May 26, 2020; Accepted June 10, 2020 
Abstract 
Inhibitory capabilities of six old drugs selected from the DrugBank database including Losartan, Triazavirin, TMC-
310911, Verapamil, Clevudine and Elbasvir, which are promising for the treatment of an infectious disease caused by 
SARS-CoV-2, were examined on the host receptor Angiotensin-converting enzyme 2 (ACE2) and the main protease 
(PDB6LU7) of SARS-CoV-2 using molecular docking simulation. Results reveal that both proteins ACE2 and 
PDB6LU7 are in strong inhibition by the drugs and the inhibitory effectiveness is in the order: Clevudine > Triazavirin 
> TMC-310911 > Elbasvir > Losartan > Verapamil. In particular, the inhibitability highly correlates with the average 
docking score energy of inhibitory complexes, and drug-protein active interactions. Regarding inhibitory ligands, their 
polarizability, molecular size, and dispersion coefficient logP are also significant indicators for inhibition potential. The 
drugs are suggested as valuable resources for selecting potential pharmaceuticals to prevent SARS-CoV-2 invasion into 
human body given theoretical demonstration of molecular docking simulation. 
Keywords. SARS-CoV-2, potential drugs, ACE2, PDB6LU7, docking simulation. 
1. INTRODUCTION 
Severe Acute Respiratory Syndrome coronavirus 2 
(SARS-CoV-2) is a new strain of coronaviruses 
family. It causes human diseases such as respiratory, 
gastrointestinal and neurological disorders, 
assembling the symptoms of the known diseases 
including Middle East Respiratory Syndrome 
(MERS-CoV) and Severe Acute Respiratory 
Syndrome (SARS).
[1-3]
 It has only been about 4 
months since the World Health Organisation (WHO) 
officially announced the first cases of infection with 
Vietnam Journal of Chemistry Nguyen Thi Ai Nhung et al. 
© 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 667 
SARS-CoV-2. They were recorded in Wuhan, 
Hubei, China. Nevertheless, there have been more 
than 3 million people worldwide confirmed positive 
with SARS-CoV-2 so far. Therefore, early finding of 
an effective treatment, conducive to the race of 
vaccine proliferation is of the goal to scientists. 
There have been hundreds of drugs applied to 
tackle acute respiratory illnesses, or infectious 
diseases. For example, Losartan is an angiotensin II 
receptor blocker (ARB), which is suggested by The 
Food and Drug Administration (FDA) of The United 
States to treat hypertension.
[4]
 Espescially, it is 
similarly used for Angiotensin-converting enzyme 
(ACE) inhibitors when a patient has a cough.
[4,5] 
Similarly, Verapamil is used to treat high blood 
pressure.
[6]
 Clevudine, also known under the trade 
names Levovir and Revovir, is an antiviral drug for 
hepatitis B treatment in South Korea and the 
Philippines. Triazavirin has been proved performing 
high efficacy towards influenza A and B, including 
the highly developed H5N1 strain
[7-10]
 in Russia. 
Because of the structural similarities between 
SARS-CoV-2 and H5N1, health officials are 
conducting studies on Triazavirin as a potential drug 
candidate to combat SARS-CoV-2.
[8]
 TMC-310911 
(known as ASC-09) is being investigated for 
fighting against various strains of HIV-1.
[11]
 Like 
other anti-HIV drugs, TMC-310911 is also being 
screened as a promising candidate to tackle SARS-
CoV-2 infection.
[12]
 Elbasvir is a direct-acting 
antiviral drug used to treat infectious liver disease 
resulted from hepatitis C virus infection.
[13]
According to Balasubramaniam and Reis (2020), 
elbasvir was theoretically calculated to create the 
best and most stable binding with the three 
important proteins essential for SARS-CoV-2 
replication.
[14]
However, there has not been any further official 
announcement about potential drugs to directly treat 
SARS-CoV-2 or its vaccine. Therefore, a study on 
the interaction mechanism between cytological 
receptors and potential drugs by docking simulation 
may initially provide useful information guiding 
preclinical experiments with a time-effecti ... x potential drugs and SARS-
CoV-2 through the amino acids of PDB6LU7 
protein are as follows: (i) Losartan forms five 
hydrogen-bond interactions with amino acids 
including Asn 142, Gln 189, His 41, Glu 166 and 
Gln 189; (ii) Triazavirin forms four hydrogen 
interactions with His 163, Asn 142, Asn 142, Gly 
143; (iii) TMC-310911 exhibits six interactions 
between the H-atom and amino acids Met 49, Met 
165, His 41, Thr 25 and Gln 189 of the main 
protease; (iv) Verapamil has four binding sites with 
some amino acids such as Cys 145, Met 165, Gly 
143, Glu 166; (v) while the amino acids Asn 142, 
Vietnam Journal of Chemistry Nguyen Thi Ai Nhung et al. 
© 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 671 
Cys 145, His 163, Asn 142, Gly 143 form hydrogen 
bonds and - bonds of Clevudin; (vi) Elbasvir 
interacts with amino acids included Cys 145, Thr 26, 
Met 165, Gln 189 of PDB6LU7 protein. 
Figure 6: SARS-CoV-2 main protease PDB6LU7 docked with the potential drugs Verapamil, Clevudine and 
Elbasvir. Docking simulation with the interaction of (A) Verapamil-PDB6LU7, (B) Clevudine-PDB6LU7 
and (C) Elbasvir-PDB6LU7 
Table 2: Docking simulation results including docking score energy (DS), root-mean-square deviation 
(RMSD), and the interaction of the 6 potential drugs and PDB6LU7 amino acids (DOI: 
10.2210/pdb6LU7/pdb) 
Drug 
Complex 
(Drug-Protein) 
DS 
(kcal·mol
-1
) 
RMSD 
(Å) 
Interaction with amino acid 
(Å) 
Losartan Losartan-PDB6LU7 -13.9 1.28 
Asn 142 (3.01), Gln 189 (3.55), 
His 41 (4.03), Glu 166 (4.66), 
Gln 189 (3.79) 
Triazavirin Triazavirin-PDB6LU7 -14.1 1.16 
His 163 (3.05), Asn 142 (3.99), 
Asn 142 (3.99), Gly 143 (3.51) 
TMC-310911 TMC-310911-PDB6LU7 -16.1 1.66 
Met 49 (3.67), Met 165 (3.94), 
His 41 (4.20), Thr 25 (4.01), Thr 
25 (3.69), Gln 189 (3.86) 
Verapamil Verapamil-PDB6LU7 -12.1 1.40 
Cys 145 (4.19), Met 165 (3.40), 
Gly 143 (3.55), Glu 166 (4.25) 
Clevudine Clevudine-PDB6LU7 -14.6 1.11 
Asn 142 (2.92), Cys 145 (3.01), 
His 163 (3.04), Asn 142 (4.60), 
Gly 143 (4.26) 
Elbasvir Elbasvir-PDB6LU7 -15.7 1.40 
Cys 145 (3.91), Thr 26 (4.46), 
Met 165 (4.13), Gln 189 (3.95) 
Furthermore, table 3 presents parameters 
obtained from the simulation, which include DSaverage 
(kcal.mol
-1
), molecular mass (Da), polarizability 
(Å
3
) and volume or size (Å) as well as the logP 
dispersion coefficient of the potential drugs and the 
total of hydrogen bonds contained in each drug-
protein inhibitory system. They were calculated by 
Gasteiger-Marsili method using QSARIS system.
[26]
It is found that the ACE2 and PDB6LU7 inhibition 
abilities of Losartan, Triazavirin, TMC-310911, 
Verapamil, Clevudin, Elbasvir exhibit the average 
DS values of -13.3, -14.1, -16.7, -11.9, -15.2 and 
-16.3 kcal.mol
-1
, respectively. Thus, Losartan and 
Verapamil show the weakest inhibition towards 
ACE2 and PDB6LU7 with the smallest DSaverage 
values of -13.3 and -11.9 kcal.mol
-1
 and the lowest 
polarizability (5.50 and 0.37 Å
3
). Whereas their 
volume significantly changes from 354.5 to 428.9 Å 
and the total of hydrogen bonds being 9 and 7 are 
also small. It is worthy to note that Verapamil shows 
Vietnam Journal of Chemistry Study on SARS-CoV-2 inhibition of 
© 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 672 
a LogP value of 5.7 being higher than 5, the value in 
which one observes weak inhibitory ability into the 
SARS-CoV-2.
[26]
Inversely, Clevudin, Triazavirin, TMC-310911 
and Elbasvir display strong inhibition towards either 
ACE2 or PDB6LU7. The larger DSaverage values 
being -14.1 and -15.2 kcal.mol
-1
 exhibit for Clevudin 
and Triazavirin. Moreover, TMC-310911 and 
Elbasvir show the strongest inhibitory effects on two 
studied proteins with the largest DSaverage values of -
16.7 and -16.3 kcal.mol
-1
 by compared with the 
other drugs in the system. Additionally, the 
polarizability values of TMC-310911 and Elbasvir 
are significantly high (i.e. 8.80 and 9.97 Debye). 
Besides, their large molecular mass and volume 
might contribute to their high binding capacity with 
amino acids. However, it is noted that Clevudine and 
Triazavirin possess the smallest molecular mass and 
large polarizability values as well as strong site-site 
binding of interactions referred to hydrogen 
bonding. Based on these observations, it can be 
affirmed that Clevudine and Triazavirin bring their 
flexibilities and large number of interactions as well 
as impressive docking score energy values. They can 
be considered as the most potential candidates of six 
studied drugs. The results may satisfy for drugs 
screening requirements under the conditions of 
Lipinski's criteria:
[27]
 (1) Molecular mass < 500 Da; 
(2) no more than 5 groups for hydrogen bonds; (3) 
no more than 10 groups receiving hydrogen bonds; 
(4) the value of logP is less than +5 (logP < 5). 
Based on the obtained results, we suggest the order 
of the potential drugs into the SARS-CoV-2 
resistance as: Clevudine > Triazavirin > TMC-
310911 > Elbasvir > Losartan > Verapamil. 
Table 3: Molecular docking parameters including the average docking score energy values 
(DSaverage, kcal.mol
-1
), molecular mass (Da), polarizability (Å
3
), volume or size (Å), logP and 
the total of hydrogen bonds of the 6 potential drugs docked with proteins ACE2 and PDB6LU7 
Drug DSaverage Mass Polarizability Volume LogP Hydrogen bond 
Losartan -13.3 422.9 5.50 354.5 3.2 9 
Triazavirin -14.1 232.2 7.88 165.8 1.1 11 
TMC-310911 -16.7 756.0 8.80 542.0 3.7 13 
Verapamil -11.9 454.6 0.37 428.9 5.7 7 
Clevudine -15.2 260.2 9.39 211.7 1.2 12 
Elbasvir -16.3 880.0 9.97 465.8 2.5 9 
4. CONCLUSION 
Docking simulation results indicate that the selected 
drugs are potential inhibitors to host receptor ACE2 
and SARS-CoV-2 main protease PDB6LU7. 
Clevudine and Triazavirin perform strongest 
inhibitability on both proteins. The respective 
inhibitability order of the active potential drugs 
towards both ACE2 and PDB6LU7 is summarized as: 
Clevudine > Triazavirin > TMC-310911 > Elbasvir > 
Losartan > Verapamil. Docking score energies of the 
drugs for inhibition of ACE2 vary from -17.2 to -11.7 
kcal.mol
-1
 and the corresponding values for 
PDB6LU7 are from -12.1 to -16.1 kcal.mol
-1
. The 
values calculated for root-mean-square deviation are 
lower than 2Å in all inhibitory systems. The potential 
drugs structurally are well-bound in their respective 
binding pose of the host receptor ACE2 and the 
targeted protease PDB6LU7. This is mainly based on 
hydrogen bond interactions between the studied 
compounds and in-pose amino acids. In particular, the 
inhibitability highly correlates with the average 
docking score energy of inhibitory complexes, and 
drug-protein active interactions. Regarding inhibitory 
ligands, their polarizability, molecular size, and 
dispersion coefficient logP are also significant 
indicators for inhibition potential. This study is highly 
conducive to further research in order to develop 
appropriate pharmaceuticals for clinical experiments 
on SARS-CoV-2. 
Acknowledgement. This research is supported by 
the Vietnam National Foundation for Science and 
Technology Development (NAFOSTED) under grant 
number 02/2020/ĐX. 
Conflict of interest. The authors declare no conflict 
of interest. 
REFERENCES 
1. X. -W. Xu, X. -X. Wu, X. -G. Jiang, K. -J. Xu, L. -J. 
Ying, C. -L. Ma, S. -B. Li, H. -Y. Wang, S. Zhang, 
H.-N. Gao. Clinical findings in a group of patients 
infected with the 2019 novel coronavirus (SARS-
Cov-2) outside of Wuhan, China: retrospective case 
Vietnam Journal of Chemistry Nguyen Thi Ai Nhung et al. 
© 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 673 
series, BMJ, 2020, 368. 
2. L. Zou, F. Ruan, M. Huang, L. Liang, H. Huang, Z. 
Hong, J. Yu, M. Kang, Y. Song, J. Xia. SARS-CoV-2 
viral load in upper respiratory specimens of infected 
patients, N. Engl. J. Med., 2020, 382, 1177-1179. 
3. J. Parry. China coronavirus: cases surge as official 
admits human to human transmission, BMJ, 2020, 
m236. 
4. M. McIntyre, S. Caffe, R. Michalak, J. Reid, 
Losartan. Losartan, an orally active angiotensin 
(AT1) receptor antagonist: a review of its efficacy 
and safety in essential hypertension, Pharmacol. 
Ther., 1997, 74, 181-194. 
5. H. M. A. Abraham, C. M. White, W. B. White. The 
comparative efficacy and safety of the angiotensin 
receptor blockers in the management of hypertension 
and other cardiovascular diseases, Drug Saf., 2015, 
38, 33-54. 
6. G. Bakris, D. Sica, V. Ram, T. Fagan, P. T. Vaitkus, 
R. J. Anders. A comparative trial of controlled-onset, 
extended-release verapamil, enalapril, and losartan on 
blood pressure and heart rate changes, Am. J. 
Hypertens., 2002, 15, 53-57. 
7. H. M. A. Abraham, C. M. White, W. B. White. 
Clevudine for the treatment of chronic hepatitis B 
virus infection, Expert Opin. Investig. Drugs, 2005, 
14, 1277-1284. 
8. M. J. Vincent, E. Bergeron, S. Benjannet, B. R. 
Erickson, P. E. Rollin, T. G. Ksiazek, N. G. Seidah, 
S. T. Nichol. Chloroquine is a potent inhibitor of 
SARS coronavirus infection and spread, Virol. J., 
2005, 2, 69. 
9. A. V. Shvetsov, Y. A. Zabrodskaya, P. A. Nekrasov, 
V.V. Egorov. Triazavirine supramolecular complexes 
as modifiers of the peptide oligomeric structure, J. 
Biomol. Struct. Dyn., 2018, 36, 2694-2698. 
10. R. M. Hoetelmans, I. Dierynck, I. Smyej, P. 
Meyvisch, B. Jacquemyn, K. Marien, K. Simmen, R. 
Verloes. Safety and pharmacokinetics of the HIV-1 
protease inhibitor TMC310911 coadministered with 
ritonavir in healthy participants: results from 2 phase 
1 studies, JAIDS J. Acquir. Immune Defic. Syndr., 
2014, 65, 299-305. 
11. H. -J. Stellbrink, K. Arastéh, D. Schürmann, C. 
Stephan, I. Dierynck, I. Smyej, R. M. Hoetelmans, C. 
Truyers, P. Meyvisch, B. Jacquemyn. Antiviral 
activity, pharmacokinetics, and safety of the HIV-1 
protease inhibitor TMC310911, coadministered with 
Ritonavir, in treatment-naive HIV-1-infected 
patients, J. Acquir. Immune Defic. Syndr., 2014, 65, 
283-289. 
12. F. Mina, M. Rahman, S. Das, S. Karmakar, M. 
Billah, Potential drug candidates underway several 
registered clinical trials for battling COVID-19. 2020 
13. S. Bagaglio, C. Uberti-Foppa, G. Morsica. Resistance 
mechanisms in hepatitis C virus: implications for 
direct-acting antiviral use, Drugs, 2017, 77, 1043-
1055. 
14. M. Balasubramaniam, R. Shmookler Reis. 
Computational target-based drug repurposing of 
elbasvir, an antiviral drug predicted to bind multiple 
SARS-CoV-2 proteins, 2020. 
15. S. R. Tipnis, N. M. Hooper, R. Hyde, E. Karran, G. 
Christie, A. J. Turner. A human homolog of 
angiotensin-converting enzyme cloning and 
functional expression as a captopril-insensitive 
carboxypeptidase, J. Bio. Chem., 2000, 275, 33238-
33243. 
16. L. E. Gralinski, V. D. Menachery. Return of the 
Coronavirus: 2019-nCoV. Viruses, 2020, 12, 135. 
17. D. Paraskevis, E. G. Kostaki, G. Magiorkinis, G. 
Panayiotakopoulos, G. Sourvinos, S. Tsiodras. Full-
genome evolutionary analysis of the novel corona 
virus (2019-nCoV) rejects the hypothesis of 
emergence as a result of a recent recombination 
event, Infect. Genet. Evol., 2020, 79, 104212. 
18. Homo Sapiens (Human). 
Https://www.Uniprot.Org/Uniprot/Q9BYF1 
19. B. T. P. Thuy, T. T. A. My, N. T. T. Hai, L. T. Hieu, 
T. T. Hoa, H. Thi Phuong Loan, N. T. Triet, T. T. V. 
Anh, P. T. Quy, P. V. Tat. Investigation into SARS-
CoV-2 resistance of compounds in garlic essential 
oil, ACS Omega, 2020. 
20. The crytal structure of COVID-19 main protease in 
complex with an inhibitor N3. 
Https://www.wwpdb.org/pdb?id=pdb_00006lu7. 
Initial deposition on: 26 January 2020. 
21. COVID information. https://www.drugbank.ca/covid-
19. 
22. O. Tarasova, V. Poroikov, A. Veselovsky. Molecular 
docking studies of HIV-1 resistance to reverse 
transcriptase inhibitors: Mini-review, Molecules, 
2018, 23, 1233. 
23. T. M. C. Babu, S. S. Rajesh, B. V. Bhaskar, S. Devi, 
A. Rammohan, T. Sivaraman, W. Rajendra, 
Molecular docking, molecular dynamics simulation, 
biological evaluation and 2D QSAR analysis of 
flavonoids from Syzygium alternifolium as potent 
anti-Helicobacter pylori agents, RSC Adv., 2017, 7, 
18277-18292. 
24. T. -D. Ngo, T. -D. Tran, M. -T. Le, K. -M. Thai. 
Computational predictive models for P-glycoprotein 
inhibition of in-house chalcone derivatives and drug-
bank compounds, Mol. Divers., 2016, 20, 945-961. 
25. K. -M. Thai, D. -P. Le, T. -D. Tran, M. -T. Le. 
Computational assay of Zanamivir binding affinity 
with original and mutant influenza neuraminidase 9 
Vietnam Journal of Chemistry Study on SARS-CoV-2 inhibition of 
© 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 674 
using molecular docking, J. Theor. Biol., 2015, 385, 
31-39. 
26. J. Gasteiger, M. Marsili. Iterative partial equalization 
of orbital electronegativity-a rapid access to atomic 
charges, Tetrahedron, 1980, 36, 3219-3228. 
27. C. A. Lipinski, F. Lombardo, B. W. Dominy, P. J. 
Feeney. Experimental and computational approaches 
to estimate solubility and permeability in drug 
discovery and development settings, Adv. Drug 
Deliv. Rev., 1997, 23, 3-25. 
Corresponding authors: Duong Tuan Quang 
University of Education, Hue University 
34, Le Loi street, Hue City 53000, Viet Nam 
E-mail: dtquang@hueuni.edu.vn 
orcid.org/0000-0002-4926-0271. 
Nguyen Thi Ai Nhung 
University of Sciences, Hue University 
77, Nguyen Hue street, Hue City 53000, Viet Nam 
E-mail: ntanhung@hueuni.edu.vn 
orcid.org/0000-0002-5828-7898.