Next Article in Journal
Respiratory and Peripheral Muscle Weakness and Body Composition Abnormalities in Non-Cystic Fibrosis Bronchiectasis Patients: Gender Differences
Previous Article in Journal
Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma
Article

Repurposing Based Identification of Novel Inhibitors against MmpS5-MmpL5 Efflux Pump of Mycobacterium smegmatis: A Combined In Silico and In Vitro Study

1
South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Bellville 7535, Cape Town, South Africa
2
Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics Russian Academy of Sciences, 119333 Moscow, Russia
3
Institute of Ecology, Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, Russia
4
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, P. Lenina 76, 454080 Chelyabinsk, Russia
5
Africa Centres for Disease Control and Prevention, African Union Headquarters, Addis Ababa W21K19, Ethiopia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Célia F. Rodrigues and Natália Cruz-Martins
Biomedicines 2022, 10(2), 333; https://doi.org/10.3390/biomedicines10020333
Received: 17 December 2021 / Revised: 25 January 2022 / Accepted: 26 January 2022 / Published: 31 January 2022
(This article belongs to the Topic Infectious Diseases)
In the current era of a pandemic, infections of COVID-19 and Tuberculosis (TB) enhance the detrimental effects of both diseases in suffering individuals. The resistance mechanisms evolving in Mycobacterium tuberculosis are limiting the efficiency of current therapeutic measures and pressurizing the stressed medical infrastructures. The bacterial efflux pumps enable the development of resistance against recently approved drugs such as bedaquiline and clofazimine. Consequently, the MmpS5-MmpL5 protein system was selected because of its role in efflux pumping of anti-TB drugs. The MmpS5-MmpL5 systems of Mycobacterium smegmatis were modelled and the virtual screening was performed using an ASINEX library of 5968 anti-bacterial compounds. The inhibitors with the highest binding affinities and QSAR based highest predicted inhibitory concentration were selected. The MmpS5-MmpL5 associated systems with BDE_26593610 and BDD_27860195 showed highest inhibitory parameters. These were subjected to 100 ns Molecular Dynamics simulations and provided the validation regarding the interaction studies. The in vitro studies demonstrated that the BDE_26593610 and BDD_27860195 can be considered as active inhibitors for M. smegmatis MmpS5-MmpL5. The outcomes of this study can be utilized in other experimentation aimed at drug design and discovery against the drug resistance strains of M. tuberculosis. View Full-Text
Keywords: tuberculosis; MmpS5-MmpL5 efflux pumps; drug resistance; virtual screening; QSAR; molecular dynamics simulations tuberculosis; MmpS5-MmpL5 efflux pumps; drug resistance; virtual screening; QSAR; molecular dynamics simulations
Show Figures

Figure 1

MDPI and ACS Style

Shahbaaz, M.; Maslov, D.A.; Vatlin, A.A.; Danilenko, V.N.; Grishina, M.; Christoffels, A. Repurposing Based Identification of Novel Inhibitors against MmpS5-MmpL5 Efflux Pump of Mycobacterium smegmatis: A Combined In Silico and In Vitro Study. Biomedicines 2022, 10, 333. https://doi.org/10.3390/biomedicines10020333

AMA Style

Shahbaaz M, Maslov DA, Vatlin AA, Danilenko VN, Grishina M, Christoffels A. Repurposing Based Identification of Novel Inhibitors against MmpS5-MmpL5 Efflux Pump of Mycobacterium smegmatis: A Combined In Silico and In Vitro Study. Biomedicines. 2022; 10(2):333. https://doi.org/10.3390/biomedicines10020333

Chicago/Turabian Style

Shahbaaz, Mohd, Dmitry A. Maslov, Aleksey A. Vatlin, Valery N. Danilenko, Maria Grishina, and Alan Christoffels. 2022. "Repurposing Based Identification of Novel Inhibitors against MmpS5-MmpL5 Efflux Pump of Mycobacterium smegmatis: A Combined In Silico and In Vitro Study" Biomedicines 10, no. 2: 333. https://doi.org/10.3390/biomedicines10020333

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop