Biochemistry
Somayeh Farahmand
Abstract
Crimean-Congo Hemorrhagic Fever (CCHF) is a zoonotic viral disease with high mortality, for which no specific and effective treatment has yet been introduced. The causative virus, classified within the Nairovirus genus and Orthonairoviridae family, encodes a polyprotein via its L segment, which includes ...
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Crimean-Congo Hemorrhagic Fever (CCHF) is a zoonotic viral disease with high mortality, for which no specific and effective treatment has yet been introduced. The causative virus, classified within the Nairovirus genus and Orthonairoviridae family, encodes a polyprotein via its L segment, which includes the RNA-dependent RNA polymerase (RdRp) and an N-terminal OTU protease domain. The OTU domain, through its deubiquitinase (DUB) activity, plays a role in suppressing the host immune response and, due to its relatively conserved sequence, represents a promising target for antiviral drug design. This study aimed to evaluate the inhibitory effect of the natural compound Phellopterin (Phe), derived from Heracleum persicum, on the OTU domain. The crystal structure of OTU (PDB ID: 3PRP) was prepared and subjected to molecular docking using AutoDock 4.0. The top-ranked complex was then analyzed via a 150-nanosecond molecular dynamics (MD) simulation using GROMACS. Phellopterin showed a favorable binding affinity (ΔG = –8.1 kcal/mol) and formed stable interactions with residues such as Ala79–Leu86 near the active-site entry. Analyses including RMSD, RMSF, Rg, hydrogen bonding, and PCA confirmed the structural stability of the complex. ADMET evaluation also indicated desirable pharmacokinetic properties, oral absorption, cellular permeability, and safety. Altogether, Phellopterin may serve as a potential inhibitor of the CCHFV OTU protease and provide a foundation for the development of effective natural antiviral agents.
Bioinformatics
Shamim Khandan Alamdari; Somayeh Farahmand; Reza Haji Hosseini; Gholamreza Bakhshi khaniki
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide, and high-risk HPV types cause about five percent of all cancers worldwide. The chemical drugs used to treat this disease are expensive and have many side effects. Therefore, the use of herbal medicines is increasing. ...
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Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide, and high-risk HPV types cause about five percent of all cancers worldwide. The chemical drugs used to treat this disease are expensive and have many side effects. Therefore, the use of herbal medicines is increasing. In this regard, the E6 protein, which is a key protein in the initiation of cervical cancer and plays a role in the degradation of P53, was selected as an essential drug target. In this research, two new potential inhibitors named beta-sitosterol (CID_222284) and loncocarpenin (CID_54699185) were identified as potent inhibitors of E6 HPV-16 from the PubChem library by high-throughput virtual screening. Molecular dynamics results show that these compounds bind to E6 protein with high stability. The preparation of ADMET and Swiss ADME profiles indicates that the identified compounds are probably potential candidates against E6 HPV-16 and can be used in chemotherapy by inhibiting the Pgp channel as an adjuvant drug.
Somayeh Farahmand; Faezeh Fatemi; Marzieh Dehghan Shasaltaneh; Reza Haji Hosseini; Shahriar Saeedyan
Abstract
In Acidithiobacillus ferrooxidans, proteins, like CoxB, present in the electron transmission pathway. The structure of CoxB has two copper atoms (CuA, CuB). CuA plays an important role in electron transport. According to previous studies, the conversion of histidine to methionine in a similar protein ...
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In Acidithiobacillus ferrooxidans, proteins, like CoxB, present in the electron transmission pathway. The structure of CoxB has two copper atoms (CuA, CuB). CuA plays an important role in electron transport. According to previous studies, the conversion of histidine to methionine in a similar protein leads to an increase the stability of protein and to improve its function. Also, the binding of methionine to CuB in the wild protein structure is another reason for the selection of the H230M mutation in CuA site. Wild-type and H230M mutants are simulated in the presence of a bilayer membrane POPC using the gromacs version 5.1.4. The conformational changes of mutated protein were investigated by RMSD, RMSF, SASA, Rg, DSSP, density, MSD, thickness, PCA, ED, DCCM and FEL analysis. The results of the wild protein and H230M mutant analysis show that the bacteria still preserves its sustainability after mutation. It seems that the H230M mutation leads to the increase of the amount of electron reception that requires further studies in this regard. Molecular dynamic simulation and principal component analysis provide compelling evidence that this H230M mutation contributes to increase the stability of protein. Thus, this finding defines new approaches in structural properties, accurate survey, and probability improves the electron transfer.
