Login Register Cart 0
Generic placeholder image

Recent Advances in Anti-Infective Drug Discovery

Editor-in-Chief

ISSN (Print): 2772-4344
ISSN (Online): 2772-4352

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Perspective

A Perspective into “TEL”-Tenofovir, Emtricitabine and Lamivudine Antileprotic Activities by Drug Repurposing and Exploring the Possibility of Combination Chemotherapy with Drug Rescued Molecules for a Leprosy Free Mankind

Author(s): Pugazhenthan Thangaraju*, Sree Sudha Tanguturi Yella, Vijayakumar Arumugam Ramamurthy, Irfan Navabshan and Thameemul Ansari Lappathai Habeeb Mohamed

Volume 18, Issue 3, 2023

Published on: 15 March, 2023

Page: [170 - 177] Pages: 8

DOI: 10.2174/2772434418666230220123217

Price: $65

Abstract

Background: Since leprosy bacilli cannot grow in vitro, testing for antimicrobial resistance against Mycobacterium leprae or assessing the anti-leprosy activity of new drugs remains hard. Furthermore, developing a new leprosy drug through the traditional drug development process is not economically captivating for pharmaceutical companies. As a result, repurposing existing drugs/approved medications or their derivatives to test their anti-leprotic potency is a promising alternative. It is an accelerated method to uncover different medicinal and therapeutic properties in approved drug molecules.

Aims: The study aims to explore the binding potential of anti-viral drugs such as Tenofovir, Emtricitabine, and Lamivudine (TEL) against Mycobacterium leprae using molecular docking.

Methods: The current study evaluated and confirmed the possibility of repurposing antiviral drugs such as TEL (Tenofovir, Emtricitabine, and Lamivudine) by transferring the graphical window of the BIOVIA DS2017 with the Crystal Structure of a phosphoglycerate mutase gpm1 from Mycobacterium leprae (PDB ID: 4EO9). Utilizing the smart minimizer algorithm, the protein's energy was reduced in order to achieve a stable local minima conformation.

Results: The protein and molecule energy minimization protocol generated stable configuration energy molecules. The protein 4EO9 energy was reduced from 14264.5 kcal/mol to -17588.1 kcal/mol.

Conclusion: The CHARMm algorithm-based CDOCKER run docked all three molecules (TEL) inside the 4EO9 protein binding pocket (Mycobacterium leprae). The interaction analysis revealed that tenofovir had a better binding molecule with a score of - 37.7297 kcal/mol than the other molecules.

« Previous Next »
Graphical Abstract

[1]
Pettit JHS, Rees RJW. Sulphone resistance in leprosy. An experimental and clinical study. Lancet 1964; 284(7361): 673-4.
[http://dx.doi.org/10.1016/S0140-6736(64)92482-1] [PMID: 14188912]
[2]
Gupta UD, Katoch K, Katoch VM. Study of rifampicin resistance and comparison of dapsone resistance of M. leprae in pre- and post-MDT era. Indian J Lepr 2009; 81(3): 131-4.
[PMID: 20509341]
[3]
Moet FJ, Pahan D, Oskam L, Richardus JH. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: Cluster randomised controlled trial. BMJ 2008; 336(7647): 761-4.
[http://dx.doi.org/10.1136/bmj.39500.885752.BE] [PMID: 18332051]
[4]
Jacobson RR, Hastings RC. Rifampin-resistant leprosy. Lancet 1976; 2(7998): 1304-5.
[http://dx.doi.org/10.1016/S0140-6736(76)92071-7]
[5]
Noordeen SK, Lopez Bravo L, Daumerie D. Global review of multidrug therapy (MDT) in leprosy. World Health Stat Q 1991; 44(1): 2-15.
[PMID: 2068821]
[6]
Cambau E, Perani E, Guillemin I, Jamet P, Ji B. Multidrug-resistance to dapsone, rifampicin, and ofloxacin in Mycobacterium leprae. Lancet 1997; 349(9045): 103-4.
[http://dx.doi.org/10.1016/S0140-6736(05)60888-4] [PMID: 8996430]
[7]
Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing challenges of leprosy. Clin Microbiol Rev 2006; 19(2): 338-81.
[http://dx.doi.org/10.1128/CMR.19.2.338-381.2006] [PMID: 16614253]
[8]
Huang F, Zhang C, Liu Q, et al. Identification of amitriptyline HCl, flavin adenine dinucleotide, azacitidine and calcitriol as repurposing drugs for influenza A H5N1 virus-induced lung injury. PLoS Pathog 2020; 16(3): e1008341.
[http://dx.doi.org/10.1371/journal.ppat.1008341] [PMID: 32176725]
[9]
Scherman D, Fetro C. Drug repositioning for rare diseases: Knowledge-based success stories. Therapie 2020; 75(2): 161-7.
[http://dx.doi.org/10.1016/j.therap.2020.02.007] [PMID: 32164975]
[10]
Sharma M, Singh P. Repurposing drugs to combat drug resistance in leprosy: A review of opportunities. Comb Chem High Throughput Screen 2022; 25(10): 1578-86.
[http://dx.doi.org/10.2174/1386207325666211007110638] [PMID: 34620073]
[11]
Balasubramaniyan S, Irfan N, Umamaheswari A, Puratchikody A. Design and virtual screening of novel fluoroquinolone analogs as effective mutant DNA GyrA inhibitors against urinary tract infection-causing fluoroquinolone resistant Escherichia coli. RSC Advances 2018; 8(42): 23629-47.
[http://dx.doi.org/10.1039/C8RA01854E] [PMID: 35540291]
[12]
Navabshan I, Sakthivel B, Pandiyan R, et al. Computational lock and key and dynamic trajectory analysis of natural biophors against COVID-19 spike protein to identify effective lead molecules. Mol Biotechnol 2021; 63(10): 898-908.
[http://dx.doi.org/10.1007/s12033-021-00358-z] [PMID: 34159564]
[13]
Thangaraju P, Venkatesan S, Showkath Ali MK. Final leprosy push: Out of society. Indian J Community Med 2018; 43(1): 58-9.
[http://dx.doi.org/10.4103/ijcm.IJCM_155_17] [PMID: 29531443]
[14]
Rosa PS, D’Espindula HRS, Melo ACL, et al. Emergence and transmission of drug/multidrug-resistant Mycobacterium leprae in a former leprosy colony in the Brazilian Amazon. Clin Infect Dis 2020; 70(10): 2054-61.
[http://dx.doi.org/10.1093/cid/ciz570] [PMID: 31260522]
[15]
Saunderson PR. Drug-resistant M. leprae. Clin Dermatol 2016; 34(1): 79-81.
[http://dx.doi.org/10.1016/j.clindermatol.2015.10.019] [PMID: 26773627]
[16]
Mahajan NP, Lavania M, Singh I, et al. Evidence for Mycobacterium leprae drug resistance in a large cohort of leprous neuropathy patients from India. Am J Trop Med Hyg 2020; 102(3): 547-52.
[http://dx.doi.org/10.4269/ajtmh.19-0390] [PMID: 31933458]
[17]
WHO Expert Committee on Leprosy: Seventh report. World Health Organization 1998.
[18]
Pai V. Second-line anti-leprosy drugs: Indian experience. Indian J Dermatol 2020; 6(1): 1.
[http://dx.doi.org/10.4103/ijdd.ijdd_66_19]
[19]
Grosset JH. Newer drugs in leprosy. Int J Lepr Other Mycobact Dis 2001; 69(2): S14-8.
[PMID: 11757174]
[20]
Balzarini J, Holy A, Jindrich J, et al. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother 1993; 37(2): 332-8.
[http://dx.doi.org/10.1128/AAC.37.2.332] [PMID: 8452366]
[21]
Tsai CC, Follis KE, Sabo A, et al. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science 1995; 270(5239): 1197-9.
[http://dx.doi.org/10.1126/science.270.5239.1197] [PMID: 7502044]
[22]
Saag MS. Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus. Clin Infect Dis 2006; 42(1): 126-31.
[http://dx.doi.org/10.1093/cid/ciu729] [PMID: 16323102]
[23]
Mu Y, Pham M, Podany AT, Cory TJ. Evaluating emtricitabine + rilpivirine + tenofovir alafenamide in combination for the treatment of HIV-infection. Expert Opin Pharmacother 2020; 21(4): 389-97.
[http://dx.doi.org/10.1080/14656566.2020.1713096] [PMID: 31957507]
[24]
Waters L, Mehta V, Gogtay J, Boffito M. The evidence for using tenofovir disoproxil fumarate plus lamivudine as a nucleoside analogue backbone for the treatment of HIV. J Virus Erad 2021; 7(1): 100028.
[http://dx.doi.org/10.1016/j.jve.2021.100028] [PMID: 33598310]
[25]
Santevecchi BA, Miller S, Childs-Kean LM. Doing more with less: Review of dolutegravir-lamivudine, a novel single-tablet regimen for antiretroviral-Naïve adults with HIV-1 infection. Ann Pharmacother 2020; 54(12): 1252-9.
[http://dx.doi.org/10.1177/1060028020933772] [PMID: 32517480]
[26]
Buchbinder SP, Liu AY. CROI 2019: Advances in HIV prevention and plans to end the epidemic. Top Antivir Med 2019; 27(1): 8-25.
[PMID: 31136999]
[27]
Clercq ED. Antivirals and antiviral strategies. Nat Rev Microbiol 2004; 2(9): 704-20.
[http://dx.doi.org/10.1038/nrmicro975] [PMID: 15372081]
[28]
Zhang S, Li N, Sheng Y, et al. Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression. Infect Agent Cancer 2021; 16(1): 20.
[http://dx.doi.org/10.1186/s13027-021-00359-2] [PMID: 33757557]
[29]
Hui VWK, Chan SL, Wong VWS, et al. Increasing antiviral treatment uptake improves survival in patients with HBV-related HCC. JHEP Reports 2020; 2(6): 100152.
[http://dx.doi.org/10.1016/j.jhepr.2020.100152] [PMID: 33024950]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy