Research Projects
Structural-guided antiviral drug and peptide design against the SARS-CoV-2
Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus (CoV-2) which infected more than 192 million individuals and resulted in more than 4.1 million fatalities. Although several vaccines are approved for covid-19 treatment, however, no small drug is approved yet and very few studies are performed for antiviral peptide therapeutics. Our long-term goal is to design, synthesize and evaluate the efficacy of highly potent and selective antiviral drug and peptides targeting the main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and spike protein (S) of SARS-CoV-2. To elucidate the mechanism of action and identify the structural determinants of potency, various techniques including native mass spectrometry, hydrogen-deuterium exchange (HDX) mass spectrometry, NMR and X-ray crystallography will be performed.
Related Publications
Chowdhury, S. M.; Talukder, S. A.; Khan, A. M.; Afrin, N.; Ali, M. A.; Islam, R.; Parves, R.; Mamun, A. A.; Sufian, M. A.; Hossain, M. N.; Hossain, M. A.; Halim, M. A. ‘Antiviral Peptides as Promising Therapeutics against SARS-CoV-2’ Journal of Physical Chemistry B, 2020, 124, 9785-9792. https://doi.org/10.1021/acs.jpcb.0c05621 Publisher: American Chemical Society, USA.
Islam, R.; Parves, R.; Paul, A. S.; Uddin, N.; Rahman, M. S.; Mamun, A. Al; Hossain, M. N.; Ali, M. A.; Halim, M. A. ‘A Molecular Modeling Approach to Identify Effective Antiviral Phytochemicals against the Main Protease of SARS-CoV-2.’ Journal of Biomolecular Structure & Dynamics 2021, 39 (9), 3213-3224. https://doi.org/10.1080/07391102.2020.1761883. Publisher: Taylor and Francis, UK
Paul, A. S.; Islam, R.; Parves, R.; Mamun, A. Al; Shahriar, I.; Hossain, M. I.; Hossain, M. N.; Ali, M. A.; Halim, M. A. ‘Cysteine focused covalent inhibitors against the main protease of SARS-CoV-2.’ Journal of Biomolecular Structure & Dynamics 2020, 1-20. In press, DOI: 10.1080/07391102.2020.1831610 Publisher: Taylor and Francis, UK
Ahmed, S.; Mahtarin, R.; Ahmed, S. S.; Akter, S.; Islam, M. S.; Mamun, A. Al; Islam, R.; Hossain, M. N.; Ali, M. A.; Sultana, M. U. C.; Halim, M. A. Investigating the Binding Affinity, Interaction, and Structure-Activity-Relationship of 76 Prescription Antiviral Drugs Targeting RdRp and Mpro of SARS-CoV-2. Journal of Biomolecular Structure & Dynamics 2020, 1–16. https://doi.org/10.1080/07391102.2020.1796804 Publisher: Taylor and Francis, UK
Rahman, M. M.; Saha, T.; Islam, K. J.; Suman, R. H.; Biswas, S.; Rahat, E. U.; Hossen, M. R.; Islam, R.; Hossain, M. N.; Mamun, A. Al; Ackas, M.; Halim, M. A. Virtual Screening, Molecular Dynamics and Structure--Activity Relationship Studies to Identify Potent Approved Drugs for Covid-19 Treatment. Journal of Biomolecular Structure & Dynamics. 2020, 1–11. https://doi.org/10.1080/07391102.2020.1794974 Publisher: Taylor and Francis, UK
Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus (CoV-2) which infected more than 192 million individuals and resulted in more than 4.1 million fatalities. Although several vaccines are approved for covid-19 treatment, however, no small drug is approved yet and very few studies are performed for antiviral peptide therapeutics. Our long-term goal is to design, synthesize and evaluate the efficacy of highly potent and selective antiviral drug and peptides targeting the main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and spike protein (S) of SARS-CoV-2. To elucidate the mechanism of action and identify the structural determinants of potency, various techniques including native mass spectrometry, hydrogen-deuterium exchange (HDX) mass spectrometry, NMR and X-ray crystallography will be performed.
Related Publications
Chowdhury, S. M.; Talukder, S. A.; Khan, A. M.; Afrin, N.; Ali, M. A.; Islam, R.; Parves, R.; Mamun, A. A.; Sufian, M. A.; Hossain, M. N.; Hossain, M. A.; Halim, M. A. ‘Antiviral Peptides as Promising Therapeutics against SARS-CoV-2’ Journal of Physical Chemistry B, 2020, 124, 9785-9792. https://doi.org/10.1021/acs.jpcb.0c05621 Publisher: American Chemical Society, USA.
Islam, R.; Parves, R.; Paul, A. S.; Uddin, N.; Rahman, M. S.; Mamun, A. Al; Hossain, M. N.; Ali, M. A.; Halim, M. A. ‘A Molecular Modeling Approach to Identify Effective Antiviral Phytochemicals against the Main Protease of SARS-CoV-2.’ Journal of Biomolecular Structure & Dynamics 2021, 39 (9), 3213-3224. https://doi.org/10.1080/07391102.2020.1761883. Publisher: Taylor and Francis, UK
Paul, A. S.; Islam, R.; Parves, R.; Mamun, A. Al; Shahriar, I.; Hossain, M. I.; Hossain, M. N.; Ali, M. A.; Halim, M. A. ‘Cysteine focused covalent inhibitors against the main protease of SARS-CoV-2.’ Journal of Biomolecular Structure & Dynamics 2020, 1-20. In press, DOI: 10.1080/07391102.2020.1831610 Publisher: Taylor and Francis, UK
Ahmed, S.; Mahtarin, R.; Ahmed, S. S.; Akter, S.; Islam, M. S.; Mamun, A. Al; Islam, R.; Hossain, M. N.; Ali, M. A.; Sultana, M. U. C.; Halim, M. A. Investigating the Binding Affinity, Interaction, and Structure-Activity-Relationship of 76 Prescription Antiviral Drugs Targeting RdRp and Mpro of SARS-CoV-2. Journal of Biomolecular Structure & Dynamics 2020, 1–16. https://doi.org/10.1080/07391102.2020.1796804 Publisher: Taylor and Francis, UK
Rahman, M. M.; Saha, T.; Islam, K. J.; Suman, R. H.; Biswas, S.; Rahat, E. U.; Hossen, M. R.; Islam, R.; Hossain, M. N.; Mamun, A. Al; Ackas, M.; Halim, M. A. Virtual Screening, Molecular Dynamics and Structure--Activity Relationship Studies to Identify Potent Approved Drugs for Covid-19 Treatment. Journal of Biomolecular Structure & Dynamics. 2020, 1–11. https://doi.org/10.1080/07391102.2020.1794974 Publisher: Taylor and Francis, UK
Detection of Gas Phase Nanostructure of Deep Eutectic Solvents by Mass Spectrometry
Deep eutectic solvents (DESs) are considered as one of the most versatile alternative media with widespread applications. DESs have the advantages of being nonflammable with negligible vapor pressure compared to the traditional solvents. They share many characteristics of ionic liquids, but DESs are cheaper to formulate, typically nontoxic, highly pure, recyclable, biodegradable, and are suitable for the biological system. In DES, two or more components are mixed at a certain ratio and form eutectic solvent through the depression of freezing point. Commonly a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD) form a complex nonbonding interaction network, inhibit the process of crystallization, and thus lower the freezing point of the solvent phase than its individual components.
Although various techniques including FT-IR, Raman, UV-Vis, NMR, TGA are used to characterize the deep eutectic solvents, no mass spectrometry experiment is reported yet. In this project, we would like to use mass spectrometry technique to detect the cluster formation of deep eutectic solvents.
Related Publications
Ali, M. A.; Rahman, M. S.; Roy, R.; Gambill, P.; Raynie, D. E.; Halim, M. A. Structure Elucidation of Menthol-Based Deep Eutectic Solvent Using Experimental and Computational Techniques. Journal of Physical Chemistry A 2021, 125 (12), 2402–2412. https://doi.org/10.1021/acs.jpca.0c10735 Publisher: American Chemical Society, USA
Saha, M.; Rahman, M. S; Hossain, M. N.; Raynie, D. E.; Halim, M. A.; ‘Molecular and Spectroscopic Insights of a Choline Chloride Based Therapeutic Deep Eutectic Solvent’ The Journal of Physical Chemistry A 2020, 124, 4690–4699. DOI: 10.1021/acs.jpca.0c00851 Publisher: American Chemical Society, USA
Rahman, M. S.; Roy, R.; Jadhav, B.; Hossain, M. N.; Halim, M. A.; Raynie, D. E. Formulation, Structure, and Applications of Therapeutic and Amino Acid-Based Deep Eutectic Solvents: An Overview. Journal of Molecular Liquids 2021, 321, 114745. https://doi.org/https://doi.org/10.1016/j.molliq.2020.114745.
Deep eutectic solvents (DESs) are considered as one of the most versatile alternative media with widespread applications. DESs have the advantages of being nonflammable with negligible vapor pressure compared to the traditional solvents. They share many characteristics of ionic liquids, but DESs are cheaper to formulate, typically nontoxic, highly pure, recyclable, biodegradable, and are suitable for the biological system. In DES, two or more components are mixed at a certain ratio and form eutectic solvent through the depression of freezing point. Commonly a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD) form a complex nonbonding interaction network, inhibit the process of crystallization, and thus lower the freezing point of the solvent phase than its individual components.
Although various techniques including FT-IR, Raman, UV-Vis, NMR, TGA are used to characterize the deep eutectic solvents, no mass spectrometry experiment is reported yet. In this project, we would like to use mass spectrometry technique to detect the cluster formation of deep eutectic solvents.
Related Publications
Ali, M. A.; Rahman, M. S.; Roy, R.; Gambill, P.; Raynie, D. E.; Halim, M. A. Structure Elucidation of Menthol-Based Deep Eutectic Solvent Using Experimental and Computational Techniques. Journal of Physical Chemistry A 2021, 125 (12), 2402–2412. https://doi.org/10.1021/acs.jpca.0c10735 Publisher: American Chemical Society, USA
Saha, M.; Rahman, M. S; Hossain, M. N.; Raynie, D. E.; Halim, M. A.; ‘Molecular and Spectroscopic Insights of a Choline Chloride Based Therapeutic Deep Eutectic Solvent’ The Journal of Physical Chemistry A 2020, 124, 4690–4699. DOI: 10.1021/acs.jpca.0c00851 Publisher: American Chemical Society, USA
Rahman, M. S.; Roy, R.; Jadhav, B.; Hossain, M. N.; Halim, M. A.; Raynie, D. E. Formulation, Structure, and Applications of Therapeutic and Amino Acid-Based Deep Eutectic Solvents: An Overview. Journal of Molecular Liquids 2021, 321, 114745. https://doi.org/https://doi.org/10.1016/j.molliq.2020.114745.
Alzheimer's Project
The Alzheimer Association® reports that ~ 5.8 million people in the U.S. suffer from Alzheimer’s disease (AD) and the number is projected to rise to 13.8 million by 2050. AD is a progressive neurodegenerative disorder causing cognitive behavioral dysfunction, impaired reasoning, and severe memory loss. Acetylcholine esterase (AChE), which hydrolyzes key neurotransmitter acetylcholine (ACh) into choline and acetate, is associated to AD disease. Targeting AChE is one of the major strategies for AD therapeutics. Some drugs, including donepezil, galantamine, memantine, rivastigmine, and tacrine are available to treat mild to moderate AD. These drugs require high doses which show moderate to severe side effects in patients. To date, AD remains incurable. Further research is required to innovate more effective drug derivatives. Several projects are available for students to conduct research on designing potent drugs using computational, cell-based and mass spectrometry approach.
Related Publications
Junaid, M.; Alam, M. J.; Hossain, M, K.; Ullah, M. O.; Halim, M. A. ‘Metal Based Donepezil Analogues Designed to Inhibit Human Acetylcholinesterase for Alzheimer's disease.’ PLOS ONE, 2019, 14(2): e0211935
*Halim, M. A.; *Pansieri, J.; Vendrely, C.; Dumoulin, M.; Moulin, M.; Chierici, S.; Denti, S.; Dagany, X.; Dugourd, P. ; Marquette, C.; Antoine, R.; Forge, V. “Mass and charge distributions of entire amyloid fibers involved in neurodegenerative diseases : Mapping polymorphism effects and population heterogeneity.” Chemical Science. 2018, 9, 2791-2796. DOI:10.1039/C7SC04542E, Publisher: Royal Society of Chemistry, UK. *Co-first author.
Rahman, A.; Ali, M. T.; Shawan, M. A. K.; Sarwar, M. G.; Khan, M. A. K. Halim, M. A.; “Halogen-directed Drug Design for Alzheimer’s disease: A Density Functional and Molecular Docking Study. SpringerPlus, 2016, 5, 1345. DOI: 10.1186/s40064-016-2996-5. Publisher: Springer, Germany
Uddin, M. J.; Russo, D.; Rahman, M. M.; Uddin, S. B.; Halim, M. A.; Zidorn, C.; Milella, L.Anticholinesterase Activity of Eight Medicinal Plant Species: In Vitro and In Silico Studies in the Search for Therapeutic Agents against Alzheimer’s Disease. Evidence-Based Complement. Altern. Med. 2021, 2021, 9995614. https://doi.org/10.1155/2021/9995614. Publisher: Hindawi, Egypt.
The Alzheimer Association® reports that ~ 5.8 million people in the U.S. suffer from Alzheimer’s disease (AD) and the number is projected to rise to 13.8 million by 2050. AD is a progressive neurodegenerative disorder causing cognitive behavioral dysfunction, impaired reasoning, and severe memory loss. Acetylcholine esterase (AChE), which hydrolyzes key neurotransmitter acetylcholine (ACh) into choline and acetate, is associated to AD disease. Targeting AChE is one of the major strategies for AD therapeutics. Some drugs, including donepezil, galantamine, memantine, rivastigmine, and tacrine are available to treat mild to moderate AD. These drugs require high doses which show moderate to severe side effects in patients. To date, AD remains incurable. Further research is required to innovate more effective drug derivatives. Several projects are available for students to conduct research on designing potent drugs using computational, cell-based and mass spectrometry approach.
Related Publications
Junaid, M.; Alam, M. J.; Hossain, M, K.; Ullah, M. O.; Halim, M. A. ‘Metal Based Donepezil Analogues Designed to Inhibit Human Acetylcholinesterase for Alzheimer's disease.’ PLOS ONE, 2019, 14(2): e0211935
*Halim, M. A.; *Pansieri, J.; Vendrely, C.; Dumoulin, M.; Moulin, M.; Chierici, S.; Denti, S.; Dagany, X.; Dugourd, P. ; Marquette, C.; Antoine, R.; Forge, V. “Mass and charge distributions of entire amyloid fibers involved in neurodegenerative diseases : Mapping polymorphism effects and population heterogeneity.” Chemical Science. 2018, 9, 2791-2796. DOI:10.1039/C7SC04542E, Publisher: Royal Society of Chemistry, UK. *Co-first author.
Rahman, A.; Ali, M. T.; Shawan, M. A. K.; Sarwar, M. G.; Khan, M. A. K. Halim, M. A.; “Halogen-directed Drug Design for Alzheimer’s disease: A Density Functional and Molecular Docking Study. SpringerPlus, 2016, 5, 1345. DOI: 10.1186/s40064-016-2996-5. Publisher: Springer, Germany
Uddin, M. J.; Russo, D.; Rahman, M. M.; Uddin, S. B.; Halim, M. A.; Zidorn, C.; Milella, L.Anticholinesterase Activity of Eight Medicinal Plant Species: In Vitro and In Silico Studies in the Search for Therapeutic Agents against Alzheimer’s Disease. Evidence-Based Complement. Altern. Med. 2021, 2021, 9995614. https://doi.org/10.1155/2021/9995614. Publisher: Hindawi, Egypt.
Breast Cancer Project
Breast Cancer (BC) is one of the most prevalent cancer types around the globe and the second leading causes of death (20.6%) in USA. In 2019, there are 271, 270 new cases reported for BC in USA, which is significantly higher than the lung and bronchus (228,150) cancer. Estrogen receptor alpha (ERα), a nuclear receptor and ligand-activated transcription factor, plays pivotal roles in treatment and prevention of the majority of BC. Due to the growing resistance of estrogen receptor gene (ESR1) in endocrine treatment, designing new drugs is now of the earnest importance. In this project, potential drug candidates will be designed against the hormone-resistance estrogen receptor (ERα) employing computational, cell and hydrogen-deuterium exchange mass spectrometry based techniques.
Related Publications
Uddin, N.; Ahmed, S.; khan, M. A. K.; Hoque, M. M.; Halim, M. A. ‘Halogenated Derivatives of Methotrexate as Human Dihydrofolate Reductase Inhibitor in Cancer Chemotherapy’ the Journal of Biomolecular Structure & Dynamics, 2020. 38 (3), 901-917. https://doi.org/10.1080/07391102.2019.1591302 Publisher: Taylor and Francis, UK
Eid, E.; Azam, F.; Hassan, M.; Taban, I.; Halim, M. A. ‘Zerumbone binding to estrogen receptors: an in-silico investigation’ Journal of Receptors and Signal Transduction, 2018, 38,342-351. DOI: 10.1080/10799893.2018.1531886 . Publisher: Taylor and Francis, UK
Tania, M.; Shawon, J.; Saif, K.; Rudolf Kiefer, R.; Khorram, M. S.; Halim, M. A.; Khan, M. A. ‘Cordycepin downregulates Cdk2 to interfere with cell cycle and increases apoptosis by generating ROS in cervical cancer cells: in vitro and in silico study’ Current Cancer Drug Target, 2019, 19,152-159 DOI: 10.2174/1568009618666180905095356 Publisher: Bentham Science, UAE.
Killoran, R. C.; Sowole, M. A.; Halim, M. A.; Konermann, L.; Choy, W.-Y. “Conformational Characterization of the Intrinsically Disordered Protein Chibby: Interplay between Structural Elements in Target Recognition” Protein Science, 2016, 25, 1420-1429. DOI: 10.1002/pro.2936. Publisher: John Wiley & Sons, USA
Rahman, A.; Hoque, M. M.; khan, M. A. K.; Sarwar, M. S.; Halim, M. A. “Non-covalent interactions involving halogenated derivatives of capecitabine and thymidylate synthase: a computational approach.” Springer Plus 2016, 5, 146. DOI: 10.1186/s40064-016-1844-y. Publisher: Springer, Germany
Saleh, M. A.; Solayman, M.; Hoque, M. M.; khan, M. A. K.; Sarwar, M. S.; Halim, M. A. “Inhibition of DNA Topoisomerase Type IIα (TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study.” Biomed Research International 2016, Article ID 6817502, 12 pages. http://dx.doi.org/10.1155/2016/6817502. Publisher: Hindawi, Egypt.
Breast Cancer (BC) is one of the most prevalent cancer types around the globe and the second leading causes of death (20.6%) in USA. In 2019, there are 271, 270 new cases reported for BC in USA, which is significantly higher than the lung and bronchus (228,150) cancer. Estrogen receptor alpha (ERα), a nuclear receptor and ligand-activated transcription factor, plays pivotal roles in treatment and prevention of the majority of BC. Due to the growing resistance of estrogen receptor gene (ESR1) in endocrine treatment, designing new drugs is now of the earnest importance. In this project, potential drug candidates will be designed against the hormone-resistance estrogen receptor (ERα) employing computational, cell and hydrogen-deuterium exchange mass spectrometry based techniques.
Related Publications
Uddin, N.; Ahmed, S.; khan, M. A. K.; Hoque, M. M.; Halim, M. A. ‘Halogenated Derivatives of Methotrexate as Human Dihydrofolate Reductase Inhibitor in Cancer Chemotherapy’ the Journal of Biomolecular Structure & Dynamics, 2020. 38 (3), 901-917. https://doi.org/10.1080/07391102.2019.1591302 Publisher: Taylor and Francis, UK
Eid, E.; Azam, F.; Hassan, M.; Taban, I.; Halim, M. A. ‘Zerumbone binding to estrogen receptors: an in-silico investigation’ Journal of Receptors and Signal Transduction, 2018, 38,342-351. DOI: 10.1080/10799893.2018.1531886 . Publisher: Taylor and Francis, UK
Tania, M.; Shawon, J.; Saif, K.; Rudolf Kiefer, R.; Khorram, M. S.; Halim, M. A.; Khan, M. A. ‘Cordycepin downregulates Cdk2 to interfere with cell cycle and increases apoptosis by generating ROS in cervical cancer cells: in vitro and in silico study’ Current Cancer Drug Target, 2019, 19,152-159 DOI: 10.2174/1568009618666180905095356 Publisher: Bentham Science, UAE.
Killoran, R. C.; Sowole, M. A.; Halim, M. A.; Konermann, L.; Choy, W.-Y. “Conformational Characterization of the Intrinsically Disordered Protein Chibby: Interplay between Structural Elements in Target Recognition” Protein Science, 2016, 25, 1420-1429. DOI: 10.1002/pro.2936. Publisher: John Wiley & Sons, USA
Rahman, A.; Hoque, M. M.; khan, M. A. K.; Sarwar, M. S.; Halim, M. A. “Non-covalent interactions involving halogenated derivatives of capecitabine and thymidylate synthase: a computational approach.” Springer Plus 2016, 5, 146. DOI: 10.1186/s40064-016-1844-y. Publisher: Springer, Germany
Saleh, M. A.; Solayman, M.; Hoque, M. M.; khan, M. A. K.; Sarwar, M. S.; Halim, M. A. “Inhibition of DNA Topoisomerase Type IIα (TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study.” Biomed Research International 2016, Article ID 6817502, 12 pages. http://dx.doi.org/10.1155/2016/6817502. Publisher: Hindawi, Egypt.
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