Uneven Expression of 20 Human Papillomavirus Genes Associated with Oropharyngeal Carcinoma.

BACKGROUND: Human papillomavirus (HPV) is considered to be responsible for 95% of virus-related cancers in many organs. Oropharyngeal carcinoma (OC) is distinguished by the transformation of the healthy epithelium into precancerous cells. AIM: The current study sought to examine the uneven gene expression of 20 genes among those scanned by microarray for oropharyngeal cancer patients. MATERIALS AND METHODS: The GSE56142 dataset was extracted from the Gene Expression Omnibus of the National Center for Biotechnology Information; 24 specimens were evaluated. Gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction (PPI) were used to depict the biological roles of the genes under investigation using types of software. RESULTS: Six genes out of 20 in patients with invasive OC had a binding correlation with high expression (PDGFRS, COL6A3, COL1A1, COL3A1, COL2A1, and COL4A1), and only two genes with low expression (CRCT1 and KRT78). The expression levels of 20 genes were examined for patients with OC versus head and neck squamous cell carcinoma (HNSCC). The correlation coefficient between highly expressed genes of the OC group was statistically significant at the P<0.05 level. CONCLUSIONS: High expression levels of specific genes may serve as diagnostic tumor markers, particularly in the early stages of cancer, and testing should be performed in OC and HNSCC patients.

Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein.

Introduction: Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. Objectives: Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. As a result, virion's effectiveness may be impaired. Results: TM can bind to viral proteins with various degrees of affinity. The proteinase had the highest binding affinity with TM. Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. ORF7a had the weakest affinities. Conclusions: This antibiotic is likely to effect on SARS-CoV-2 in clinical studies.

Introducción: A pesar de la disponibilidad de varias vacunas contra la COVID-19, la incidencia de infecciones sigue siendo un problema grave. La tunicamicina (TM), un antibiótico, inhibió el crecimiento tumoral, redujo la síntesis de la subunidad 2 de la glicoproteína de la envoltura del coronavirus y disminuyó la glicosilación ligada a N de las glicoproteínas del coronavirus. Objetivos: Nuestro estudio tuvo como objetivo determinar cómo interactúa la tunicamicina con ciertas proteínas del coronavirus (proteinasa, proteasa, nsp9, ORF7a, ORF3a, ORF9b, ORF8, proteína de la envoltura, nsp2 y RBD de glicoproteína de punta). Métodos: Se utilizaron varios tipos de herramientas de quimioterapia y bioinformática para lograr el objetivo del estudio. Como resultado, la eficacia del virión puede verse afectada. Resultados: La TM puede unirse a proteínas virales con diversos grados de afinidad. La proteinasa tenía la mayor afinidad de unión con TM. Las proteínas (ORF9b, ORF8, nsp9 y RBD) se vieron afectadas por enlaces donantes o aceptores desfavorables que afectan el grado de acoplamiento. ORF7a tenía las afinidades más débiles. Conclusiones: Es probable que este antibiótico tenga efecto sobre el SARS-CoV-2 en estudios clínicos.

The efficacy of Paxlovid against COVID-19 is the result of the tight molecular docking between Mpro and antiviral drugs (nirmatrelvir and ritonavir).

PURPOSE: Currently, a number of medications for coronavirus disease 2019 (COVID-19) treatment are tested in clinical trials; however, credible clinical studies are becoming increasingly difficult to come by. Paxlovid is a ritonavir-boosted nirmatrelvir drug that the U.S. Food and Drug Administration (FDA) authorized for the treatment of COVID-19. This study aimed to demonstrate the interaction of nirmatrelvir and ritonavir on the active site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). MATERIALS AND METHODS: To locate the optimal docking between Mpro and antiviral drugs, and to conduct dynamic simulations between atoms in the fusion areas, various bioinformatics and mathematical equations were applied. RESULTS: According to the docking data, nirmatrelvir has a stronger interaction with Mpro than ritonavir, which has more multiple bonds. Molecular docking of antiviral drugs such as Paxlovid has a significant impact on the treatment of COVID-19 virus. CONCLUSIONS: According to this study, Paxlovid may work on new strains, including Omicron, because the Mpro mutation P132H in the Omicron variant has no direct effect on the protein.

La mutación N15Y en la proteína E del coronavirus 2 del síndrome respiratorio agudo severo afecta la unión de doxiciclina y rutina / The N15Y mutation in the E protein of severe acute respiratory syndrome coronavirus 2 affects the binding of doxycycline and rutin

The severe acute respiratory syndrome coronavirus 2 genetic variation must be closely monitored. Viral transmission can inevitably result from mutations in the viral genome and functional proteins that aid in the virus's adaptation to the host. This study aimed to look for mutations in the E protein and see how they affected the ligands' molecular docking. Mathematical saturation mutagenesis and other informatics techniques were used. Fourteen severe acute respiratory syndrome coronavirus 2 isolates from Iraq were selected. Doxycycline and rutin were chosen as ligands. In four strains of severe acute respiratory syndrome coronavirus 2, the N15Y mutation was detected in the envelope protein. Depending on the calculation of the amount of energy of the atoms, this mutation is critical in modifying the shape of the protein as well as increasing protein stability. In the single-chain mutation, one pocket was determined, while all pentamer chains had two pockets. The N15Y mutation altered the degree of doxycycline binding by affecting the residue of attachment of the ligands. It also altered the position of the rutin's attachment to the E protein, which has a clear impact on the virion particle(AU)

La variación genética del coronavirus 2 del síndrome respiratorio agudo severo debe ser monitoreada de cerca. La transmisión viral puede resultar inevitablemente de mutaciones en el genoma viral y proteínas funcionales que ayudan en la adaptación del virus al hospedero. Este estudio tuvo como objetivo buscar mutaciones en la proteína E y ver cómo afectaban el acoplamiento molecular de los ligandos. Se utilizó la mutagénesis de saturación matemática y otras técnicas informáticas. Se seleccionaron 14 aislamientos del coronavirus 2 del síndrome respiratorio agudo severo en Irak. Se eligieron doxiciclina y rutina como ligandos. En cuatro cepas del coronavirus 2 del síndrome respiratorio agudo severo, se detectó la mutación N15Y en la proteína de la envoltura. Dependiendo del cálculo de la cantidad de energía de los átomos, esta mutación es fundamental para modificar la forma de la proteína y aumentar la estabilidad de la proteína. En la mutación de cadena única, se determinó un bolsillo, mientras que todas las cadenas de pentámero tenían dos bolsillos. La mutación N15Y alteró el grado de unión de doxiciclina al afectar el residuo de unión de los ligandos. También alteró la posición de unión de la rutina a la proteína E, lo que tiene un claro impacto en la partícula del virión(AU)

Implementation of immuno-chemoinformatics approaches to construct multi-epitope for vaccine development against Omicron and Delta SARS-CoV-2 variants.

Background: The new coronavirus is still a life-threatening menace, because of its changing nature and capacity to produce many mutations to bypass the immune system. The vaccination is the first effective weapon against COVID-19. Aim: The study's goal was to design a multi-epitope peptide vaccine (MEPV) for a mix of Omicron and Delta Coronavirus strains using immuno-chemoinformatics tools. Methods: To create the vaccine epitopes, seven proteins from the Omicron and Delta coronavirus strains were selected (ORF1a, ORF3a, surface protein, membrane protein, ORF7a, ORF8, and nucleocapsid protein). Antigenicity, toxicity, and allergenicity of the epitopes were evaluated. Results: The designed vaccine is made up of 534 amino acids that are homogeneous, antigenic, and non-toxic. Sticky restriction enzymes (XhoI and XbaI) were used to incorporate the MEPV into the pmirGLO luciferase vector. SnapGene server was used to create primers for PCR testing. Developing the MEPV is a terrific cost-effective strategy. The created MEPV's physiochemical properties have been determined to be basic, hydrophobic, and stableImmunogenicity and immune response profiles of the developed vaccine candidate were better assessed using in silico immunological simulations. Conclusions: We advocate moving the built vaccine to the biological validation step, where it may test our findings using appropriate model organisms.

Antecedentes: el nuevo coronavirus sigue siendo una amenaza mortal debido a su naturaleza cambiante y su capacidad de producir muchas mutaciones para eludir el sistema inmunitario. La vacunación es la primera arma eficaz contra el COVID-19. Objetivo: el objetivo del estudio era diseñar una vacuna peptídica multiepítopo (MEPV) para una mezcla de cepas de Omicron y Delta Coronavirus utilizando herramientas inmunoquimioinformáticas. Métodos: Para crear los epítopos de la vacuna, se seleccionaron siete proteínas de las cepas de coronavirus Omicron y Delta (ORF1a, ORF3a, proteína de superficie, proteína de membrana, ORF7a, ORF8 y proteína de nucleocápside). Se evaluaron la antigenicidad, toxicidad y alergenicidad de los epítopos. Resultados: La vacuna diseñada está compuesta por 534 aminoácidos que son homogéneos, antigénicos y no tóxicos. Se usaron enzimas de restricción pegajosas (XhoI y XbaI) para incorporar el MEPV en el vector de luciferasa pmirGLO. El servidor SnapGene se utilizó para crear cebadores para las pruebas de PCR. Desarrollar el MEPV es una excelente estrategia rentable. Se ha determinado que las propiedades fisicoquímicas del MEPV creado son básicas, hidrofóbicas y estables. Se utilizaron simulaciones inmunológicas in silico para evaluar mejor la inmunogenicidad y el perfil de respuesta inmunitaria de la vacuna candidata generada. Conclusiones: Abogamos por pasar la vacuna construida al paso de validación biológica, donde puede probar nuestros hallazgos utilizando organismos modelo apropiados.

Increasing the frequency of omicron variant mutations boosts the immune response and may reduce the virus virulence.

The coronavirus has posed a serious threat to the world since its discovery in Wuhan in 2019. Beta, gamma, delta, and the final omicron variants have emerged as a result of several mutations in the virion structure. The Australian Omicron S protein variant contains 37 mutations out of a total of 67 mutations. According to preliminary data from South Africa, Omicron variant infection is not associated with any particular symptoms. The purpose of this research was to determine how changes in the structure of the S protein alter the protein's interaction with the ACE2 receptor. The Omicron variant stimulates the immune response more than the wild strain.

Inhibition of N-linked Glycosylation by Tunicamycin May Contribute to The Treatment of SARS-CoV-2.

SARS-CoV-2 remains a medical and economic challenge, due to the lack of a suitable drug or vaccine. The glycans in some proteins play a pivotal role in protein folding, oligomerization, quality control, sorting, and transport so the hindering of N-linked glycosylation of glycoproteins will prevent assembly of the virion. Tunicamycin an anticancer drug inhibit the N- linked glycans. Our study aimed to find out the mechanism action of tunicamycin on the viral glycoproteins. The growth of coronavirus in the presence inhibitor tunicamycin resulted in the production of spikeless, non-infectious virions which were devoid of S protein. We concluded that tunicamycin inhibits E2, S, and M glycoproteins of coronaviruses. Tunicamycin is also diminished glycosylation of PTMs such as HE, and 8 ab of SARS-CoV. Finally, we recommend using this drug to treat the SARS-CoV-2.