Broad-Spectrum Inhibitor Discovery Targeting Coronavirus Nucleocapsid Proteins via 3D Structure-Based Virtual Screening and Molecular Dynamics Ebtisam Aldaais, Munthir Aldukhi, Hind Alotaibi, Heba Mofleh Alzabni, Subha Yegnaswamy, Nada F. Alahmady Covid, 2026 Rapid antigenic drift in the coronavirus spike protein motivates alternative antiviral strategies. We target the conserved nucleocapsid (N) protein—central to RNA binding, genome packaging, and replication—and perform a comparative, cross-species 3D structure-based in silico evaluation. A library of 494 compounds (natural, phytochemical, synthetic) was docked with AutoDock Vina against the MERS-CoV N–terminal RNA–binding domain (NTD; PDB 7DYD) and the C–terminal dimerization domains (CTD) of SARS-CoV (2CJR) and SARS-CoV-2 (8R6E), reflecting the availability of high-resolution, functionally relevant domain structures for each virus. Top-ranked poses underwent ADME profiling and 100 ns GROMACS molecular-dynamics (MD) simulations. Myricetin 3-O-β-D-Galactopyranoside (myricetin) showed the most favorable predicted docking scores across targets (−8.9 kcal/mol, MERS–NTD; −10.1, SARS–CTD; −9.8, SARS-CoV-2 CTD). Curcumin showed moderate predicted affinity (−7.1 to −8.1), while MCC950 achieved consistently favorable docking score (−7.9 to −9.0). ADME results highlighted a trade-off: glycosylated flavonoids offered rich interaction networks but violated oral drug-likeness criteria (e.g., high TPSA), whereas MCC950 met Lipinski/Veber guidelines, supporting translational potential. MD analyses revealed ligand- and target-specific stability: myricetin maintained persistent binding over 100 ns in the SARS-CoV-2 CTD with lower RMSD than comparators; curcumin exhibited transient stability (~30 ns) in MERS- and SARS-bound complexes; MCC950 showed intermittent interactions. Collectively, these findings suggest that the conserved N protein RNA-binding groove represents a resistance-resilient target for broad-spectrum antiviral discovery. Natural flavonoids provide promising scaffolds for optimization, and MCC950 warrants further exploration given its drug-like profile. As this study is purely computational, the results are hypothesis-generating and should be validated via RNA-binding disruption assays, antiviral cell studies, and in vivo models.
Conformational dynamics of the membrane protein of MERS-CoV in comparison with SARS-CoV-2 in ERGIC complex Subha Yegnaswamy, Selvaa Kumar C., Ebtisam Aldaais Journal of Biomolecular Structure and Dynamics, 2026 The present study explores the conformational dynamics of the membrane protein of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within the Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC) complex using an all-atomistic molecular dynamics simulation approach. Significant structural changes were observed in the N-terminal, C-terminal, transmembrane, and beta-sheet sandwich domains of the MERS-CoV membrane protein. This study also highlights the structural similarities between the MERS-CoV and the SARS-CoV-2 membrane proteins, particularly in how both exhibit a distinct kink in the transmembrane helix caused by aromatic residue-lipid interactions. A structural expansion below the transmembrane and above the beta-sheet sandwich domain within the dimer was observed in all the M-proteins. This site on the beta-sheet sandwich domains near the C-terminal end could serve as a potential drug-binding site. Notably, a stable helical structure was identified in the C-terminal domain of the MERS-CoV membrane protein, whereas a proper secondary structural conformation was not observed in the SARS-CoV-2 membrane protein. Further, the SARS-CoV-2 membrane protein exhibited stronger binding to the lipid bilayer than the MERS-CoV, indicating its greater structural stability within the ERGIC complex. The structural similarity between the membrane protein of MERS-CoV and SARS-CoV-2 suggests the feasibility of employing a common inhibitor against these beta-coronaviruses. Furthermore, this analysis enhances our understanding of the membrane protein's interactions with proteins and lipids, paving the way for therapeutic developments against these viruses.
Structural resilience of conserved-site mutations in the MERS-CoV membrane protein: insights into stability and conformational dynamics Subha Yegnaswamy, Selvaa Kumar C, Ebtisam Aldaais, Isha Shinde Journal of Biomolecular Structure and Dynamics, 2026 MERS-CoV remains a significant global health challenge due to sporadic outbreaks. The ongoing emergence of new viral variants, particularly among betacoronaviruses, underscores the importance of understanding mutations in structural proteins. The membrane (M) protein, a highly conserved structural component essential for viral assembly, is a promising target for therapeutic intervention, and any mutations in this protein are particularly concerning as they may compromise antiviral efficacy. Despite its critical role, the structural consequences of M protein mutations remain poorly characterised. This study investigates six conserved amino-acid substitutions (F27L, A62T, V69L, I82T, T127I, and R162H) identified in the M- protein across bat coronaviruses, SARS-related coronaviruses, and MERS-CoV. Using atomistic molecular dynamics simulations, we examined how these substitutions affect MERS-CoV M protein stability, dimerisation, and interaction with the N protein. All mutants largely preserved native-like structural stability relative to the wild type, indicating that the M protein is resilient to mutation-induced alterations at conserved sites. Although the R162H substitution within the β-sheet domain induced localised flexibility, it did not result in substantial global conformational changes. Notably, the I82T mutant identified exhibited structural stability similar to the wild-type protein, supporting its evolutionary persistence. Furthermore, the mutant M proteins maintained favourable dimeric interactions and stable binding with the N protein. Collectively, these findings elucidate how conserved-site mutations modulate M-protein dynamics while preserving structural and functional integrity, potentially contributing to coronavirus adaptability.
Evaluation of X-ray radiation shielding performance of Bi2O3 and BaTiO3 embedded in PVP and PEG polymer nanocomposite O. Bawazeer, Bayan Baatiyah, Shatha Al Amoudi, Zubeda Aga, Zeinab Matar, Suha Khan, Saeed Al-Qahtani, Merfat Algethami, Syed Farooq Adil, Ali-Hanan Alomari, M. Althomali, E. Aldaais, Abdulwali Ajlouni Radiation Effects and Defects in Solids, 2025 This study addressed the limitations of lead-based radiation shields by developing lead-free, non-toxic, lightweight, and flexible shielding materials with high attenuation efficiency. To achieve this, single and triple layers of Bi<sub>2</sub>O<sub>3</sub>-BaTiO<sub>3</sub>/PVP-PEG nanocomposite films were synthesized. Polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) polymers (2:1 ratio) were used as the polymeric matrix in which fillers of Bi<sub>2</sub>O<sub>3</sub> and BaTiO<sub>3</sub> nanoparticles (NPs) with particle sizes ranging from 90 to 210 nm and <100 nm, respectively, were embedded. Four single-layer samples with 20%, 30%, 40%, and 50% NP concentrations were prepared; the samples were 1.05, 1.09, 1.27, and 1.42 mm thick, respectively. Two samples of triple-layered films were prepared with 30% and 50% NPs, measuring 3.78 and 4.23 mm in thickness, respectively. The attenuation efficiency of these films was investigated using X-ray tube voltages from 10 to 120 kVp. Further, the flexibility of the synthesized films was tested by manual handling. All single- and triple-layer nanocomposites exhibited effective radiation attenuation and desirable flexibility. Specifically, at the lowest tube voltage, all samples exhibited 100% attenuation, while at the highest tube voltage, the attenuation ranged from 27% to 84%, depending on the NP concentration and number of layers of the sample. The highest attenuation ratio, observed in the 50% triple-layer sample, reached 100% up to approximately 60 kVp and 84% at 120 kVp. Consequently, the most optimal film synthesized in this study had a triple-layer configuration with 50% Bi<sub>2</sub>O<sub>3</sub>-BaTiO<sub>3</sub> NPs embedded in a PVP-PEG polymer with an average attenuation of 95.5% for all tube voltages (10–120 kVp). Therefore, this shielding is suitable for various diagnostic applications, such as mammography, dental X-rays, computerized tomography, and fluoroscopy. <b>Highlights</b>Single- and triple-layered nanocomposite Bi<sub>2</sub>O<sub>3</sub>-BaTiO<sub>3</sub>/PVP-PEG films were synthesizedThe attenuation efficiency of the films against X-rays was investigatedA triple-layer configuration with 50% Bi<sub>2</sub>O<sub>3</sub>-BaTiO<sub>3</sub>/PVP-PEG was suitable for various diagnostic applications Single- and triple-layered nanocomposite Bi<sub>2</sub>O<sub>3</sub>-BaTiO<sub>3</sub>/PVP-PEG films were synthesized The attenuation efficiency of the films against X-rays was investigated A triple-layer configuration with 50% Bi<sub>2</sub>O<sub>3</sub>-BaTiO<sub>3</sub>/PVP-PEG was suitable for various diagnostic applications
The Actual Role of Iterative Reconstruction Algorithm Methods in Several Saudi Hospitals As A Tool For Radiation Dose Minimization of Ct Scan Examinations Haney Alsleem, Abdulrahman Tajaldeen, Abdulrahman Almutairi, Hussain Almohiy, Ebtisam Aldaais, Rayan Albattat, Mousa Alsleem, Elfatih Abuelhia, Osama Abdalla Mabrouk Kheiralla, Ahmed Alqahtani, Salem Alghamdi, Rowa Aljondi, Renad Alharbi Journal of Multidisciplinary Healthcare, 2022 Background Iterative reconstruction algorithm (IR) techniques were developed to maintain a lower radiation dose for patients as much as possible while achieving the required image quality and medical benefits. The main purpose of the current research was to assess the level and usage extent of IR techniques in computed tomographic (CT) scan exams. Also, the obligation of practitioners in several hospitals in Saudi Arabia to implement IR in CT exams was assessed. Material and Methodology The recent research was based on two studies: data collection and a survey study. Data on the CT scan examinations were retrospectively collected from CT scanners. The survey was conducted using a questionnaire to evaluate radiographers’ and radiologists’ perceptions about IR and their practices with IR techniques. The statistical analysis results were performed to measure the usage strength level of IR methods. Results and Discussions The IR strength level of 50% was selected for nearly 80% of different CT examinations and patients of different ages and weights. About 46% of the participants had not learned about IR methods during their college studies, and 54% had not received formal training in applying IR techniques. Only 32% of the participants had adequate experience with IR. Half of the participants were not involved in the updating process of the CT protocol. Conclusion The results indicate that the majority of radiographer and radiologist at four different hospitals in Saudi Arabia have no explicit or understandable knowledge of selecting IR strength levels during the CT examination of patients. There is a need for more training in IR applications for both radiologists and radiographers. Training sessions were suggested to support radiographers and radiologists to efficiently utilize IR techniques to optimize image quality. Further studies are required to adjust CT exam protocols effectively to utilize the IR technique.
Sequence and structural analysis of COVID-19 E and M proteins with MERS virus E and M proteins—A comparative study Ebtisam A. Aldaais, Subha Yegnaswamy, Fatimah Albahrani, Fatima Alsowaiket, Sarah Alramadan Biochemistry and Biophysics Reports, 2021 The outbreak of SARS in 2003, MERS in 2012, and now COVID-19 in 2019 have demonstrated that Coronaviruses are capable of causing primary lethal infections in humans, and the pandemic is now a global concern. The COVID-19 belongs to the beta coronavirus family encoding 29 proteins, of which four are structural, the Spike, Membrane, Envelope, and Nucleocapsid proteins. Here we have analyzed and compared the Membrane (M) and Envelope (E) proteins of COVID-19 and MERS with SARS and Bat viruses. The sequence analysis of conserved regions of both E and M protein revealed that many regions of COVID-19 are similar to Bat and SARS viruses while the MERS virus showed variations. The essential binding motifs found in SARS appeared in COVID-19. Besides, the M protein of COVID-19 showed a distinct serine phosphorylation site in the C-terminal domain, which looked like a catalytic triad seen in serine proteases. A Dileucine motif occurred many times in the sequence of the M protein of all the four viruses compared. Concerning the structural part, the COVID-19 E protein showed more similarity to Bat while MERS shared similarity with the SARS virus. The M protein of both COVID-19 and MERS displayed variations in the structure. The interaction between M and E protein was also studied to know the additional binding regions. Our study highlights the critical motifs and structural regions to be considered for further research to design better inhibitors for the infection caused by these viruses.
New method of increased accuracy for the calculation of intermolecular interactions in thermotropic polymers Ebtisam A. Aldaais Results in Materials, 2019 Thermotropic polymeric tissues have attracted considerable scientific interest for their useful biomedical applications. The complex coupling of van der Waals and steric interactions influences the thermal response of polymers’ molecular structure. Comprehensive theories that govern the molecular reorganization define the intramolecular interactions as the interactions between segments of the same polymer, and intermolecular interactions as the interactions between different polymers' segments of differ. The attractive interactions between polymer segments are determined via exact calculations of the intramolecular interactions, while the intermolecular interactions are treated with a self-consistent approximation, which leads to the double counting of the intermolecular interactions. Our decoupled self-consistent field theory (SCF) corrects for that double counting. The results show that the decoupled SCF theory considers less attractive energy than the standard one. These results improve the calculations of several parameters, such as the polymers end-to-end distance, and distinguish the critical parameters that lead to the formation of micelles.
Conformational dynamics of the membrane protein of MERS-CoV in comparison with SARS-CoV-2 in ERGIC complex S Yegnaswamy, SK C, E Aldaais Journal of Biomolecular Structure and Dynamics 44 (6), 2975-2989 , 2026 2026 Citations: 2
Broad-Spectrum Inhibitor Discovery Targeting Coronavirus Nucleocapsid Proteins via 3D Structure-Based Virtual Screening and Molecular Dynamics E Aldaais, M Aldukhi, H Alotaibi, HM Alzabni, S Yegnaswamy, ... COVID 6 (3), 36 , 2026 2026
Structural resilience of conserved-site mutations in the MERS-CoV membrane protein: insights into stability and conformational dynamics S Yegnaswamy, SK C, E Aldaais, I Shinde Journal of Biomolecular Structure and Dynamics, 1-22 , 2026 2026
Cellulose-based and polysaccharide delivery systems for phytochemicals in MERS-CoV and SARS-CoV-2 treatment: A systematic review of therapeutic potential EA Aldaais International Journal of Biological Macromolecules 313, 143985 , 2025 2025 Citations: 1
Evaluation of X-ray radiation shielding performance of Bi 2 O 3 and BaTiO 3 embedded in PVP and PEG polymer nanocomposite O Bawazeer, B Baatiyah, S Al Amoudi, Z Aga, Z Matar, S Khan, ... Radiation Effects and Defects in Solids 180 (3-4), 463-475 , 2025 2025 Citations: 7
Meta-analysis of polyethylene glycol and cellulose-based polymers in vaccine and drug delivery: A comprehensive review EA Aldaais Preprints , 2023 2023 Citations: 1
A comprehensive review on the COVID-19 vaccine and drug delivery applications of interpenetrating polymer networks EA Aldaais Drug Delivery and Translational Research 13 (3), 738-756 , 2023 2023 Citations: 5
Meta-Analysis of Polyethylene Glycol and Cellulose-based Polymers in Vaccine and Drug Delivery: A Comprehensive EA Aldaais 2023
The actual role of iterative reconstruction algorithm methods in several Saudi hospitals as a tool for radiation dose minimization of CT scan examinations H Alsleem, A Tajaldeen, A Almutairi, H Almohiy, E Aldaais, R Albattat, ... Journal of Multidisciplinary Healthcare, 1747-1757 , 2022 2022 Citations: 2
Sequence and structural analysis of COVID-19 E and M proteins with MERS virus E and M proteins—A comparative study EA Aldaais, S Yegnaswamy, F Albahrani, F Alsowaiket, S Alramadan Biochemistry and biophysics reports 26, 101023 , 2021 2021 Citations: 29
From Modeling Free Chains with the Rosenbluth Algorithm to Modeling Rigid, Compact, and Overlapped Chains with Our Developed Algorithm E Aldaais, S Crittenden Bulletin of the American Physical Society 65 , 2020 2020
Industrial Chemistry: Open Access EA Aldaais, SA Almaghrabi, MM Alabdullah 2020
Generalizing Rosenbluth's Algorithm to Include Along‐the‐Chain Intramolecular Energies EA Aldaais, S Crittenden Journal of Polymer Science Part B: Polymer Physics 57 (24), 1684-1691 , 2019 2019 Citations: 1
New method of increased accuracy for the calculation of intermolecular interactions in thermotropic polymers EA Aldaais Results in Materials 1, 100013 , 2019 2019 Citations: 3
Contributing to Vision 2030 with a Saudi Polymer Research Center EA Aldaais J Nanomed Nanotechnol 10 (1), 527 , 2019 2019
Generalized Theory of Monoligand-Receptor Binding for the Improvement of Nanoparticle Design EA Aldaais Journal of Nanomedicine & Nanotechnology 9 (4) , 2018 2018 Citations: 4
A theoretical study of polymer based drug delivery systems EA Aldaais University of South Carolina , 2016 2016 Citations: 6
A Theoretical Study of Polymer-Based Drug Delivery Systems EA Aldaais, MJ Uline Biophysical Journal 108 (2), 633a-634a , 2015 2015
A Theoretical Study of The Coupling Between Chemical Equilibrium and Physical Interactions That Determine Self-Organization in End-Grafted Polyelectrolytes for Tissue-Material … E Aldaais, M Uline Bulletin of the American Physical Society 59 , 2014 2014
SU‐E‐T‐389: Accuracy of a VMAT Planning System for Head and Neck Radiotherapy E Aldaais, D Tedeschi, W Gebreamlak, T Shieder, H Alkhatib Medical Physics 39 (6Part16), 3793-3794 , 2012 2012 Citations: 1
MOST CITED SCHOLAR PUBLICATIONS
Sequence and structural analysis of COVID-19 E and M proteins with MERS virus E and M proteins—A comparative study EA Aldaais, S Yegnaswamy, F Albahrani, F Alsowaiket, S Alramadan Biochemistry and biophysics reports 26, 101023 , 2021 2021 Citations: 29
Evaluation of X-ray radiation shielding performance of Bi 2 O 3 and BaTiO 3 embedded in PVP and PEG polymer nanocomposite O Bawazeer, B Baatiyah, S Al Amoudi, Z Aga, Z Matar, S Khan, ... Radiation Effects and Defects in Solids 180 (3-4), 463-475 , 2025 2025 Citations: 7
A theoretical study of polymer based drug delivery systems EA Aldaais University of South Carolina , 2016 2016 Citations: 6
A comprehensive review on the COVID-19 vaccine and drug delivery applications of interpenetrating polymer networks EA Aldaais Drug Delivery and Translational Research 13 (3), 738-756 , 2023 2023 Citations: 5
Generalized Theory of Monoligand-Receptor Binding for the Improvement of Nanoparticle Design EA Aldaais Journal of Nanomedicine & Nanotechnology 9 (4) , 2018 2018 Citations: 4
New method of increased accuracy for the calculation of intermolecular interactions in thermotropic polymers EA Aldaais Results in Materials 1, 100013 , 2019 2019 Citations: 3
Conformational dynamics of the membrane protein of MERS-CoV in comparison with SARS-CoV-2 in ERGIC complex S Yegnaswamy, SK C, E Aldaais Journal of Biomolecular Structure and Dynamics 44 (6), 2975-2989 , 2026 2026 Citations: 2
The actual role of iterative reconstruction algorithm methods in several Saudi hospitals as a tool for radiation dose minimization of CT scan examinations H Alsleem, A Tajaldeen, A Almutairi, H Almohiy, E Aldaais, R Albattat, ... Journal of Multidisciplinary Healthcare, 1747-1757 , 2022 2022 Citations: 2
Cellulose-based and polysaccharide delivery systems for phytochemicals in MERS-CoV and SARS-CoV-2 treatment: A systematic review of therapeutic potential EA Aldaais International Journal of Biological Macromolecules 313, 143985 , 2025 2025 Citations: 1
Meta-analysis of polyethylene glycol and cellulose-based polymers in vaccine and drug delivery: A comprehensive review EA Aldaais Preprints , 2023 2023 Citations: 1
Generalizing Rosenbluth's Algorithm to Include Along‐the‐Chain Intramolecular Energies EA Aldaais, S Crittenden Journal of Polymer Science Part B: Polymer Physics 57 (24), 1684-1691 , 2019 2019 Citations: 1
SU‐E‐T‐389: Accuracy of a VMAT Planning System for Head and Neck Radiotherapy E Aldaais, D Tedeschi, W Gebreamlak, T Shieder, H Alkhatib Medical Physics 39 (6Part16), 3793-3794 , 2012 2012 Citations: 1
Broad-Spectrum Inhibitor Discovery Targeting Coronavirus Nucleocapsid Proteins via 3D Structure-Based Virtual Screening and Molecular Dynamics E Aldaais, M Aldukhi, H Alotaibi, HM Alzabni, S Yegnaswamy, ... COVID 6 (3), 36 , 2026 2026
Structural resilience of conserved-site mutations in the MERS-CoV membrane protein: insights into stability and conformational dynamics S Yegnaswamy, SK C, E Aldaais, I Shinde Journal of Biomolecular Structure and Dynamics, 1-22 , 2026 2026
Meta-Analysis of Polyethylene Glycol and Cellulose-based Polymers in Vaccine and Drug Delivery: A Comprehensive EA Aldaais 2023
From Modeling Free Chains with the Rosenbluth Algorithm to Modeling Rigid, Compact, and Overlapped Chains with Our Developed Algorithm E Aldaais, S Crittenden Bulletin of the American Physical Society 65 , 2020 2020
Industrial Chemistry: Open Access EA Aldaais, SA Almaghrabi, MM Alabdullah 2020
Contributing to Vision 2030 with a Saudi Polymer Research Center EA Aldaais J Nanomed Nanotechnol 10 (1), 527 , 2019 2019
A Theoretical Study of Polymer-Based Drug Delivery Systems EA Aldaais, MJ Uline Biophysical Journal 108 (2), 633a-634a , 2015 2015
A Theoretical Study of The Coupling Between Chemical Equilibrium and Physical Interactions That Determine Self-Organization in End-Grafted Polyelectrolytes for Tissue-Material … E Aldaais, M Uline Bulletin of the American Physical Society 59 , 2014 2014