Browsing by Author "Ghosh, Arabinda"

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Abetting Host Immune Response by Inhibiting Rhipicephalus sanguineus Evasin-1
(Daffodil International University, 22-09-13) Castrosanto, Melvin A.; Mukerjee, Nobendu; Ramos, Ana Rose; Maitra, Swastika; Manuben, John Julius P.; Das, Padmashree; Malik, Sumira; Hasan, Mohammad Mehedi; Alexiou, Athanasios; Dey, Abhijit; Kamal, Mohammad Amjad; Aljarba, Nada H.; Alkahtani, Saad; Ghosh, Arabinda
The brown dog tick (Rhipicephalus sanguineus) is the most prevalent tick in the world and a well-recognized vector of many pathogens affecting dogs and occasionally humans. Pathogens exploit tick salivary molecules for their survival and multiplication in the vector and transmission to and establishment in the hosts. Tick saliva contains various non-proteinaceous substances and secreted proteins that are differentially produced during feeding and comprise of inhibitors of blood congealing and platelet aggregation, vasodilatory and immunomodulatory substances, and compounds preventing itch and pain. One of these proteins is Evasin-1, which has a high binding affinity to certain types of chemokines. The binding of Evasin-1 to chemokines prevents the detection and immune response of the host to R. sanguineus, which may result in the successful transmission of pathogens. In this study, we screened potential Evasin-1 inhibitor based on the pharmacophore model derived from the binding site residues. Hit ligands were further screened via molecular docking and virtual ADMET prediction, which resulted in ZINC8856727 as the top ligand (binding affinity: -9.1 kcal/mol). Molecular dynamics simulation studies, coupled with MM-GBSA calculations and principal component analysis revealed that ZINC8856727 plays a vital role in the stability of Evasin-1. We recommend continuing the study by developing a formulation that serves as a potential medicine aid immune response during R. sanguineus infestation.
COVID-19 Diagnostic Methods in Developing Countries
(Daffodil International University, 2022-05-27) Maniruzzaman, Md.; Islam, Md. Missile; Ali, Md. Hazrat; Mukerjee, Nobendu; Maitra, Swastika; Kamal, Mohammad Amjad; Ghosh, Arabinda; Castrosanto, Melvin A.; Alexiou, Athanasios; Ashraf, Ghulam Md.; Tagde, Priti; Rahman, Md. Habibur
COVID-19 has become one of the few leading causes of death and has evolved into a pandemic that disrupts everyone’s routine, and balanced way of life worldwide, and will continue to do so. To bring an end to this pandemic, scientists had put their all effort into discovering the vaccine for SARS-CoV-2 infection. For their dedication, now, we have a handful of COVID-19 vaccines. Worldwide, millions of people are at risk due to the current pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite the lack of clinically authorized antiviral medications and vaccines for COVID-19, clinical trials of many recognized antiviral agents, their combination, and vaccine development in patients with confirmed COVID-19 are still ongoing. This discovery gave us a chance to get immune to this disease worldwide and end the pandemic. However, the unexpected capacity of mutation of the SARS-CoV-2 virus makes it difficult, like the recent SAS-CoV-2 Omicron variant. Therefore, there is a great necessity to spread the vaccination programs and prevent the spread of this dreadful epidemic by identifying and isolating afflicted patients. Furthermore, several COVID-19 tests are thought to be expensive, time-consuming, and require the use of adequately qualified persons to be carried out efficiently. In addition, we also conversed about how the various COVID-19 testing methods can be implemented for the first time in a developing country and their cost-effectiveness, accuracy, human resources requirements, and laboratory facilities.
Mechanistic Inhibition of Monkeypox and Marburg Virus Infection by O-Rhamnosides and Kaempferol-O-Rhamnosides Derivatives
(Frontier Scientific Publishing, 2023-05-24) Mashud, Md Abdullah Al; Kumer, Ajoy; Mukerjee, Nobendu; Chandro, Akhel; Maitra, Swastika; Chakma, Unesco; Dey, Abhijit; Akash, Shopnil; Alexiou, Athanasiosis; Khan, Azmat Ali; Alanazi, Amer M; Ghosh, Arabinda; Chen, Kow-Tong; Sharma, Rohit
"The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study's primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses."
Modified Coptisine Derivatives as an Inhibitor Against Pathogenic Rhizomucor miehei, Mycolicibacterium smegmatis (Black Fungus), Monkeypox, and Marburg Virus by Molecular Docking and Molecular Dynamics Simulation-Based Drug Design Approach
(Frontier Scientific Publishing, 2023-04-19) Akash, Shopnil; Hossain, Arafat; Mukerjee, Nobendu; Sarker, Md. Moklesur Rahman; Khan, Mohammad Firoz; Hossain, Md. Jamal; Rashid, Mohammad A.; Kumer, Ajoy; Ghosh, Arabinda; León-Figueroa, Darwin A.; Barboza, Joshuan J.; Padhi, Bijaya Kumar; Sah, Ranjit
"During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our in silico investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg viruses."
Recognizing Novel Drugs against Keap1 in Alzheimer's disease Using Machine Learning Grounded Computational Studies
(Scopus, 22-12-31) Mukerjee, Nobendu; Al-Khafaji, Khattab; Maitra, Swastika; Wadi, Jaafar Suhail; Sachdeva, Punya; Ghosh, Arabinda; Buchade, Rahul Subhash; Chaudhari, Somdatta Yashwant; Jadhav, Shailaja B.; Das, Padmashree; Hasan, Mohammad Mehedi; Rahman, Md. Habibur; Albadrani, Ghadeer M.; Albadrani, M.; Altyar, Ahmed E.; Kamel, Mohamed; Algahtani, Mohammad; Shinan, Khlood; Theyab, Abdulrahman; Daim, Mohamed M. Abdel-; Ashraf, Md.; Rahman, Md. Mominur; Sharma, Rohit
Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer’s disease. We chose the ursolic acid (UA) and its similar compounds as a compounds’ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (QSAR) model was created by evaluating standard machine learning techniques, and the best model has the lowest RMSE and greatest R2 (Random Forest Regressor). We chose pIC50 of 6.5 as threshold, where the top five potent medicines (DB06841, DB04310, DB11784, DB12730, and DB12677) with the highest predicted pIC50 (7.091184, 6.900866, 6.800155, 6.768965, and 6.756439) based on QSAR analysis. Furthermore, the top five medicines utilize as ligand molecules were docked in Keap1’s binding region. The structural stability of the nominated medications was then evaluated using molecular dynamics simulations, RMSD, RMSF, Rg, and hydrogen bonding. All models are stable at 20 ns during simulation, with no major fluctuations observed. Finally, the top five medications are shown as prospective inhibitors of Keap1 and are the most promising to battle AD.
Repurposing Food Molecules as a Potential BACE1 Inhibitor for Alzheimer's Disease
(Daffodil International University, 2022-08-22) Mukerjee, Nobendu; Das, Anubhab; Jawarkar, Rahul D.; Maitra, Swastika; Das, Padmashree; Castrosanto, Melvin A.; Paul, Soumyadip; Samad, Abdul; Zaki, Magdi E. A.; Al-Hussain, Sami A.; Masand, Vijay H.; Hasan, Mohammad Mehedi; Bukhari, Syed Nasir Abbas; Perveen, Asma; Alghamdi, Badrah S.; Alexiou, Athanasios; Kamal, Mohammad Amjad; Dey, Abhijit; Malik, Sumira; Bakal, Ravindra L.; Abuzenadah, Adel Mohammad; Ghosh, Arabinda; Ashraf, Ghulam Md
Alzheimer’s disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of β-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave β-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of β-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R2 = 0.82, Q2loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = −8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate’s inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.
Target Specific Inhibition of West Nile Virus Envelope Glycoprotein and Methyltransferase Using Phytocompounds
(Frontier Scientific Publishing, 2023-06-28) Akash, Shopnil; Bayıl, Imren; Rahman, Md. Anisur; Mukerjee, Nobendu; Maitra, Swastika; Islam, Md. Rezaul; Rajkhowa, Sanchaita; Ghosh, Arabinda; Al-Hussain, Sami A.; Zaki, Magdi E. A.; Jaiswal, Vikash; Sah, Sanjit; Barboza, Joshuan J.; Sah, Ranjit
"Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus’s ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from −7.4 to −8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from −6.2 to −8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical. "