Hira Khalid

@bzu.edu.pk

Department of Biochemistry, Bahauddin Zakariya University, Multan
Bahauddin Zakariya University, Multan

Hira Khalid


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https://researchid.co/hirakhalid

EDUCATION

I am a distinguished biochemistry graduate with a strong academic foundation and focused research expertise in computer-aided drug design (CADD), evidenced by multiple publications in high-impact, peer-reviewed journals. My research contributions reflect a dedication to scientific rigor, innovation, and advancement in molecular science.

RESEARCH, TEACHING, or OTHER INTERESTS

Biochemistry, Clinical Biochemistry, Immunology and Microbiology, Pharmacology, Toxicology and Pharmaceutics
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Scopus Publications

Scopus Publications

  • Bacterial Metabolite-Derived NDM-1 Inhibitors: A Computational Strategy to Overcome β-Lactam Resistance
    Bader S. Alotaibi, Farhat Shabbir, Muhammad Umer Khan, Iqra Ahmad, Hira Khalid, Shahid Aziz, Abid Ali, Sonia Younas, Hanna Dib, Khaled Fahmi Fawy, Umar Nishan, Mohibullah Shah
    Probiotics and Antimicrobial Proteins, 2026
  • Computational Profiling of Asteraceae-Derived Phytochemicals Targeting S-Adenosylhomocysteine Hydrolase (SAHH) of Naegleria fowleri
    Hira Khalid, Iqra Ahmad, Muhammad Hassan Butt, Amen Shamim, Umar Nishan, Abid Ali, Hanna Dib, Aqal Zaman, Mohibullah Shah
    Chemistryselect, 2025
    Primary amoebic meningoencephalitis (PAM) is a rare but fatal disease caused by Naegleria fowleri ( N. fowleri ). This parasitic amoeba has adverse and deadly effects on humans and animals, as it thrives in fresh and warm water environments and has a mortality rate of up to 95%. The pathogen's resistance to current pharmacological regimens, even in combination drug therapies, is a major contribution to its high mortality. The current study aimed to investigate the potential of antiparasitic plants of the Asteraceae family for inhibiting N. fowleri's S‐adenosyl‐homocysteine hydrolase enzyme (Nf‐SAHH). An in‐house library of 716 natural products was obtained from selected ayurvedic antiparasitic plants and virtually screened against Nf‐SAHH. The identified hits were subjected to initial evaluation based on standard drug‐likeness criteria and ligand efficiency. Stability between the interacting residues of the target receptor and the top active ligands was further confirmed by molecular dynamic simulation. Our six top‐screened hits, namely, 3‐hexadecyloxy carbonyl‐5‐(2‐hydroxyethyl)‐4‐methyl imidazolium ion (HCEMI), geranylgeraniol (GGOH), hexadecanoic acid, 2‐hydroxy‐1‐(hydroxymethyl) ethyl ester, (+)‐sesamin (+)‐arborone, and octadecanoic acid 2,3‐dihydroxypropyl ester showed docking score greater than adenosine analogue (Neplanocin A). These inhibitors also adhered to established drug‐likeness criteria, demonstrating favorable ligand efficiency, pharmacophoric and pharmacokinetic properties. They exhibited stable results in molecular dynamics simulations with a broad spectrum of biological activities. Moreover, the concentration–time profile of HCEMI and geranylgeraniol indicated significant concentrations of these metabolites in the brain tissue to bind and inhibit Nf‐SAHH. Their activities extended beyond their robust affinity for the target protein. Predominantly non‐mutagenic, most of the hits possess the capability to permeate the blood–brain barrier (BBB). They inhibit the P‐glycoprotein, making them viable candidates for treating PAM infection. Given their potential to effectively inhibit the Nf‐SAHH protein, these hits warrant further investigation through in vitro and in vivo studies for the development of novel drugs against the PAM infection.
  • Screening Asian Medicinal Plants for SARS-CoV-2 Inhibitors: A Computational Approach
    Hira Khalid, Iqra Ahmad, Asifa Sarfraz, Anwar Iqbal, Umar Nishan, Hanna Dib, Riaz Ullah, Sheheryar Sheheryar, Mohibullah Shah
    Chemistry and Biodiversity, 2025
    This work aimed to evaluate the antiviral potential of compounds from Asian medicinal plants against SARS‐CoV‐2's main protease and spike glycoprotein, identifying dual inhibitors from these plants that target both proteins through advanced virtual screening, molecular dynamics simulations, and pharmacophore analysis. An in‐house library of 335 antiviral natural products was prepared from the selected medicinal plants. Following the virtual screening of this library against the main protease and spike glycoprotein, top compounds were subjected to downstream analysis for evaluating druggability potential and toxicity analysis. Molecular dynamic simulations were performed to confirm the stability of interactions between the ligands and target proteins. Our analysis demonstrated 67 compounds as dual inhibitors. The six top dual inhibitors, namely trans‐delta‐viniferin, trans‐E‐viniferin, 3,4‐DHPEA‐EDA, oleuropein aglycone, lactucopicrin, and 11β,13‐dihydrolactucopicrin, exhibited superior docking scores and met drug‐likeness criteria, including Lipinski's rule, bioavailability, and favorable ADME and toxicity profiles. Trans‐delta‐viniferin and trans‐E‐viniferin, featuring a stilbene scaffold, emerged as the most promising candidates due to their stable interactions, minimal fluctuations, and consistent hydrogen bonding across SARS‐CoV‐2's Mpro and S‐protein in MD simulations, while 3,4‐DHPEA‐EDA displayed comparatively less stability. All compounds demonstrated key pharmacophoric features and lacked mutagenicity or PAINS alerts, although lactucopicrin and 11β,13‐dihydrolactucopicrin showed risks for hepatotoxicity. Overall, the critical bonding and drug‐like features, biological activity spectra, and favorable medicinal characteristics predict their biological behavior in laboratory testing. Although additional experimental validations are necessary, our findings indicate that the three lead compounds—namely, trans‐delta‐viniferin, trans‐E‐viniferin, and 3,4‐DHPEA‐EDA, isolated from traditional medicinal plants—are promising novel dual inhibitors of two critical SARS‐CoV‐2 proteins.
  • Phytobioinformatics screening of ayurvedic plants for potential α-glucosidase inhibitors in diabetes management
    Hira Khalid, Muhammad Hassan Butt, Aziz ur Rehman Aziz, Iqra Ahmad, Farzana Iqbal, Amen Shamim, Umar Nishan, Riaz Ullah, Mohamed A. Ibrahim, Arlindo Alencar Moura, Mohibullah Shah, Wenwen Sun
    Current Plant Biology, 2024
    The enzyme α-glucosidase in the small intestine regulates blood glucose levels and stimulates the hydrolysis of oligosaccharides and polysaccharides, increasing glucose levels in the body. Inhibiting this enzyme slows glucose digestion and absorption and as a result post-prandial blood glucose levels remain low, causing decreased insulin demand. Here, we investigated the ayurvedic antidiabetic plants and virtually screened an in-house library of 478 phytochemicals of these plants against the human α-glucosidase. We identified 11 secondary metabolites, including palmitic acid α-monoglyceride, (+)-(2 R)-6-propionyloxyethyl-4′,5,7-trihydroxyisoflavanone, Abruquinone E, and Aurantiamide Acetate, among others, showed stronger interactions with the receptor than the native ligand N-acetyl cysteine. Surprisingly, except one, all of these metabolites were from Abrus precatorius L. [Fabaceae] affirming its ethnopharmacological use against diabetes. The stability of the interactions between the ligands and receptor protein was evaluated through Molecular Dynamic (MD) simulation trajectories including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), H bonds, β-factor analysis, and binding energy calculation through MM/GBSA method. The efficacy of top metabolites in inhibiting α-glucosidase is depicted in pharmacophore analysis. A comprehensive pharmacokinetics analysis confirmed the druggability, safety, and efficiency of top drug candidates. Additionally, we predicted the interactions of these top metabolites within the biological system. The medicinal properties described in this study will help develop active drug candidates for therapeutic purposes. Further experiments are recommended to prove the effectiveness of these metabolites in inhibiting the α-glucosidase enzyme for exploring their potential in the treatment of diabetes. • In-house library of 478 phytochemicals from selected ayurvedic plants was generated. • Eleven metabolites showed stronger interactions with the receptor proteins compare to the N-acetyl cysteine. • The stability of the interactions between the ligands and receptor protein was evaluated through molecular dynamics simulation trajectories including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), H bonds, β-factor analysis, and binding energy calculation through MM/GBSA method. T • A comprehensive ADMET analysis was performed to confirm the druggability, safety, and efficiency of the top drug candidates. • The interactions of the top metabolites within the biological system were determined.
  • Identification of Novel Quinolone and Quinazoline Alkaloids as Phosphodiesterase 10A Inhibitors for Parkinson’s Disease through a Computational Approach
    Iqra Ahmad, Hira Khalid, Asia Perveen, Muhammad Shehroz, Umar Nishan, Faiz Ur Rahman, Sheheryar, Arlindo Alencar Moura, Riaz Ullah, Essam A. Ali, Mohibullah Shah, Suvash Chandra Ojha
    ACS Omega, 2024
    Phosphodiesterases (PDEs) are vital in signal transduction, specifically by hydrolyzing cAMP and cGMP. Within the PDE family, PDE10A is notable for its prominence in the striatum and its regulatory function over neurotransmitters in medium-spiny neurons. Given the dopamine deficiency in Parkinson’s disease (PD) that affects striatal pathways, PDE10A inhibitors could offer therapeutic benefits by modulating D1 and D2 receptor signaling. This study was motivated by the successful history of quinazoline/quinazoline scaffolds in the inhibition of PDE10A. This study involved detailed in silico evaluations through docking followed by pharmacological, pharmacophoric, and pharmacokinetic analyses, prioritizing central nervous system (CNS)-active drug criteria. Seven cyclic peptides, those featuring the quinazoline/quinazoline moiety at both termini, exhibited notably enhanced docking scores compared to those of the remaining alkaloids within the screened library. We identified 7 quinolines and 1 quinazoline including Lepadin G, Aspernigerin, CJ-13536, Aurachin A, 2-Undecyl-4(1H)-quinolone, Huajiaosimuline 3-Prenyl-4-prenyloxyquinolin-2-one, and Isaindigotone that followed the standard CNS active drug criteria. The dominant quinoline ring in our study and its related quinazoline were central to our evaluations; therefore, the pharmacophoric features of these scaffolds were highlighted. The top alkaloids met all CNS-active drug properties; while nonmutagenic and without PAINS alerts, many indicated potential hepatotoxicity. Among the compounds, Huajiaosimuline was particularly significant due to its alignment with lead-likeness and CNS-active criteria. Aspernigerin demonstrated its affinity for numerous dopamine receptors, which signifies its potential to alter dopaminergic neurotransmission that is directly related to PD. Interestingly, the majority of these alkaloids had biological targets primarily associated with G protein-coupled receptors, critical in PD pathophysiology. They exhibit superior excretion parameters and toxicity end-points compared to the standard. Notably, selected alkaloids demonstrated stability in the binding pocket of PDE10A according to the molecular dynamic simulation results. Our findings emphasize the potential of these alkaloids as PDE10A inhibitors. Further experimental studies may be necessary to confirm their actual potency in inhibiting PDE10A before exploring their therapeutic potential in PD.
  • Computer-assisted discovery of natural inhibitors for platelet-derived growth factor alpha as novel therapeutics for thyroid cancer
    Hira Khalid, Farah Sattar, Iqra Ahmad, Valdir Ferreira de Paula Junior, Umar Nishan, Riaz Ullah, Hanna Dib, Khaled W. Omari, Mohibullah Shah
    Frontiers in Pharmacology, 2024
    Platelet-derived growth factor alpha (PDGFRA) plays a significant role in various malignant tumors. PDGFRA expression boosts thyroid cancer cell proliferation and metastasis. Radiorefractory thyroid cancer is poorly differentiated, very aggressive, and resistant to radioiodine therapy. Thus, novel anticancer drugs that inhibit its metastasis are urgently required. In this context, we proposed the PDGFRA inhibitors by an optimized structure-based drug design approach. We performed a virtual screening of metabolites derived from anticancer medicinal plants (Swertia chirayita, Myristica fragrans, and Datura metel) and successfully identified seven hits, namely cis-Grossamide K, Daturafoliside O, N-cis-feruloyltyramine, Maceneolignan H, Erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(3, 4, 5-trimethoxyphenyl) propan-1, 3-diol, Myrifralignan C, and stigmasteryl-3-O-β-glucoside as potential PDGFRA inhibitors. Not only the top 7 hits exhibited higher docking scores in docking simulation but also optimal drug-likeness and non-toxic profiles in pharmacokinetics analysis among 119 compounds. Our top hits are non-mutagenic, can cross the blood-brain barrier, and inhibit p-glycoprotein, while the N-cis-feruloyltyramine has the potential to become a lead compound. The protein-ligand stability of the top 3 hits, namely cis-Grossamide K, Daturafoliside O, and N-cis-feruloyltyramine, and their interactions at the potential binding site of target protein were confirmed through molecular dynamic simulations. We also analyzed pharmacophoric features for stable binding in the PDGFRA active site. These drug candidates were further characterized to predict their biological activity spectra in the human body and medicinal characteristics to know their extensive behavior in laboratory testing. This study necessitates the in-vitro and in-vivo studies to confirm the potential of our hits for the discovery of novel therapeutics against the thyroid cancer.
  • Identifying plant-derived antiviral alkaloids as dual inhibitors of SARS-CoV-2 main protease and spike glycoprotein through computational screening
    Ramsha Yamin, Iqra Ahmad, Hira Khalid, Asia Perveen, Sumra Wajid Abbasi, Umar Nishan, Sheheryar Sheheryar, Arlindo Alencar Moura, Sarfraz Ahmed, Riaz Ullah, Essam A. Ali, Mohibullah Shah, Suvash Chandra Ojha
    Frontiers in Pharmacology, 2024
    COVID-19 is currently considered the ninth-deadliest pandemic, spreading through direct or indirect contact with infected individuals. It has imposed a consistent strain on both the financial and healthcare resources of many countries. To address this challenge, there is a pressing need for the development of new potential therapeutic agents for the treatment of this disease. To identify potential antiviral agents as novel dual inhibitors of SARS-CoV-2, we retrieved 404 alkaloids from 12 selected medicinal antiviral plants and virtually screened them against the renowned catalytic sites and favorable interacting residues of two essential proteins of SARS-CoV-2, namely, the main protease and spike glycoprotein. Based on docking scores, 12 metabolites with dual inhibitory potential were subjected to drug-likeness, bioactivity scores, and drug-like ability analyses. These analyses included the ligand–receptor stability and interactions at the potential active sites of target proteins, which were analyzed and confirmed through molecular dynamic simulations of the three lead metabolites. We also conducted a detailed binding free energy analysis of pivotal SARS-CoV-2 protein inhibitors using molecular mechanics techniques to reveal their interaction dynamics and stability. Overall, our results demonstrated that 12 alkaloids, namely, adouetine Y, evodiamide C, ergosine, hayatinine, (+)-homoaromoline, isatithioetherin C, N,alpha-L-rhamnopyranosyl vincosamide, pelosine, reserpine, toddalidimerine, toddayanis, and zanthocadinanine, are shortlisted as metabolites based on their interactions with target proteins. All 12 lead metabolites exhibited a higher unbound fraction and therefore greater distribution compared with the standards. Particularly, adouetine Y demonstrated high docking scores but exhibited a nonspontaneous binding profile. In contrast, ergosine and evodiamide C showed favorable binding interactions and superior stability in molecular dynamics simulations. Ergosine demonstrated exceptional performance in several key pharmaceutical metrics. Pharmacokinetic evaluations revealed that ergosine exhibited pronounced bioactivity, good absorption, and optimal bioavailability. Additionally, it was predicted not to cause skin sensitivity and was found to be non-hepatotoxic. Importantly, ergosine and evodiamide C emerged as superior drug candidates for dual inhibition of SARS-CoV-2 due to their strong binding affinity and drug-like ability, comparable to known inhibitors like N3 and molnupiravir. This study is limited by its in silico nature and demands the need for future in vitro and in vivo studies to confirm these findings.