MOLECULAR SIMULATION AND STOCHASTIC DOMINANCE ANALYSIS OF LIGANDS IN DRUGS FOR TREATMENT OF TB/HIV USING THE WEIGHTED GAMMA-RAYLEIGH DISTRIBUTION

ENO EMMANUELLA  AKARAWAK; MARADESA  ADELEKE; DIMA TESTIMONY  AKARAWAK

ENO EMMANUELLA AKARAWAK DEPARTMENT OF STATISTICS, UNIVERSITY OF LAGOS, NIGERIA
MARADESA ADELEKE DEPARTMENT OF MECHANICAL ENGINEERING, HONG KONG UNIVERSITY OF SCIENCE AND TECHNOLOGY, HONG KONG
DIMA TESTIMONY AKARAWAK DEPARTMENT OF CHEMICAL ENGINEERING, UNIVERSITY OF LAGOS, NIGERIA

Keywords: Weighted Gamma-Rayleigh Distribution, Stochastic Dominance, Ligands, Binding Affinity

Abstract

The recent treatment for Tuberculosis involves a prolonged study of a combination of antibiotics with toxic side-effects and is associated with poor patient compliance. This has resulted to the multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of M. tuberculosis. The number of anti-TB drugs currently in the pipeline is insufficient to address this major health challenge. Therefore, there is an urgent need to discover and develop new and efficient drugs against TB. Studying the interaction and functioning of drug components is the first step in the discovery process and Molecular docking is one of the methods that have been used to study drug interaction and functioning. In this study, a molecular dynamics simulation study of ligands (Ethambutol, Isoniazid, Rifampicin, Streptomycin, Pyrazinamides) that are responsible for the effectiveness of Anti-TB/HIV therapy was carried out. Additionally, the Weighted Gamma-Rayleigh distribution (WGRD) is introduced in this research work, and used in testing the stochastic dominance of the binding affinity of the ligands to the Anti-TB/HIV drugs. Results showed that Rifampicin has higher binding affinity as it has (first order stochastically) dominated Streptomycin and Pyrazinamide. Isoniazid has (first order stochastically) dominated Ethambutol. Also, Isoniazid has great power in reducing toxicity of Anti-TB/HIV drug. The results from this study provide an avenue for good health policy and prospective planning, especially in Anti-TB/HIV drug development.

References

[1] World Health Organization (WHO) (2023). Global Tuberculosis Report. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2023/tb-disease-burden/1-1-tb-incidence, retrieved 13/10/2024
[2] World Health Organization (WHO) (2014). Malaria Fact Sheet No 94. 2014. Retrieved 25/6/2015.
[3] Ryu, Y. J. (2015). Diagnosis of Pulmonary Tuberculosis: Recent Advances and Diagnostic Algorithms. Tuberc Respir Dis (Seoul). Apr;78(2):64-71. doi: 10.4046/trd.2015.78.2.64. Epub 2015 Apr 2. PMID: 25861338; PMCID: PMC4388902.
[4] Asgharzadeh, M., Kafil, H. S., & Pourostadi, M. (2014). Limited transmission of multidrug-resistant tuberculosis in East Azarbaijan, Iran.BeniSuef Univ. J. Basic Appl. Sci. 3, 254–259. doi: 10.1016/j.bjbas.2014. 11.004.
[5] Zumla, A., Nahid, P., & Cole, S.T (2013). Advances in the development of new tuberculosis drugs and treatment regimens.Nat Rev Drug Discov, 12(5):388–404.
[6] Kanagaraj, B., Wadhwa, D. and Prakash, A. (2014). Molecular Docking of Lung Cancer Proteins Against Specific Drug Targets. World Journal of Pharmaceutical Research, Volume 3, Issue 3, 4248-4262
[7] Agu, P.C., Afiukwa, C.A., Orji, O.U., Ezeh, E.M., Ofoke, I.H., Ogbu, C.O., Ugwuja, E.I. and Aja, P.M. (2023). Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci Rep 13, 13398. https://doi.org/10.1038/s41598-023-40160-2
[8] Vincent S, Arokiyaraj S, Saravanan M and Dhanraj M (2020) Molecular Docking Studies on the Anti-viral Effects of Compounds from Kabasura Kudineer on SARS-CoV-2 3CLpro. Front. Mol. Biosci. 7:613401. doi: 10.3389/fmolb.2020.613401
[9] Akarawak, E.E.E., Adeleke, A.I., & Okafor, R.O., (2017). Gamma-Rayleigh Distribution with Application to Survival Data, Nigerian Journal of Basic and Applied Science, 25(2):130-142.
[10] Patil, G.P. and Rao, C.R. (1978) Weighted Distributions and Size-Biased Sampling with Applications to Wildlife Populations and Human Families. Biometrics, 34, 179-189. http://dx.doi.org/10.2307/2530008
[11] Syed, A., Muhammad, H., Muhammad, U., Rana, M., Shahid, M., Khalid, A., Muhammad, B. & Muhammad, Z. (2019). A Molecular Docking Approach to Evaluate the Pharmacological Properties of Natural and Synthetic Treatment Candidates for Use against Hypertension, International Journal of Environmental Research and Public Health, 16:923-956
[12] Adejoro, I.A., Waheed, S.O., & Adeboye O.O. (2016). Molecular Docking Studies of Lonchocarpus cyanescens Triterpenoids as Inhibitors for Malaria; .Journal of Physical Chemistry and Biophysics, 6: 2; doi:10.4172/2161-0398.1000213.