RESUMEN
Viruses change the host cell metabolism to produce infectious particles and create optimal conditions for replication and reproduction. Numerous host cell pathways have been modified to ensure available biomolecules and sufficient energy. Metabolomics studies conducted over the past decade have revealed that eukaryotic viruses alter the metabolism of their host cells on a large scale. Modifying pathways like glycolysis, fatty acid synthesis and glutaminolysis could provide potential energy for virus multiplication. Thus, almost every virus has a unique metabolic signature and a different relationship between the viral life cycle and the individual metabolic processes. There are enormous research in virus induced metabolic reprogramming of host cells that is being conducted through numerous approaches using different vaccine candidates and antiviral drug substances. This review provides an overview of viral interference to different metabolic pathways and improved monitoring in this area will open up new ways for more effective antiviral therapies and combating virus induced oncogenesis.
Asunto(s)
Virus , Humanos , Redes y Vías Metabólicas , Glucólisis , Replicación ViralRESUMEN
SARS-CoV-2 is a single-stranded RNA (+) virus first identified in China and then became an ongoing global outbreak. In most cases, it is fatal in humans due to respiratory malfunction. Extensive researches are going to find an effective therapeutic technique for the treatment of SARS-CoV-2 infected individuals. In this study, we attempted to design a siRNA molecule to silence the most suitable nucleocapsid(N) gene of SARS-CoV-2, which play a major role during viral pathogenesis, replication, encapsidation and RNA packaging. At first, 270 complete N gene sequences of different strains in Bangladesh of these viruses were retrieved from the NCBI database. Different computational methods were used to design siRNA molecules. A siRNA molecule was built against these strains using the SiDirect 2.0 server. Using Mfold and the OligoCalc server, the siRNA molecule was tested for its secondary structure and GC material. The Clustal Omega tool was employed to evaluate any off-target harmony of the planned siRNA molecule. Herein, we proposed a duplex siRNA molecule that does not fit any off-target sequences for the gene silencing of SARS-CoV-2. To treat SARS-CoV-2 infections, currently, any effective therapy is not available. Our engineered siRNA molecule could give an alternative therapeutic approach against various sequenced SARS-CoV-2 strains in Bangladesh.
Asunto(s)
COVID-19/virología , Proteínas de la Nucleocápside de Coronavirus/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacología , SARS-CoV-2/genética , Bangladesh/epidemiología , COVID-19/epidemiología , Simulación por Computador , Proteínas de la Nucleocápside de Coronavirus/genética , Regulación Viral de la Expresión Génica , Humanos , Modelos QuímicosRESUMEN
Chikungunya virus (CHIKV) instigating Chikungunya fever is a global infective menace resulting in high fever, weakened joint-muscle pain, and brain inflammation. Inaccessibility and unavailability of effective drugs have led us to an uncertain arena when it comes to providing proper medical treatment to the affected people. In this study, authentic encroachment has been made concerning the peptide-based epitope vaccine designing against CHIKV. A Proteome-wide search was performed to locate a conserved portion among the accessible viral outer membrane proteins which showcase a remarkable immune response using specific immunoinformatics and docking simulation tools. Primarily, the most probable immunogenic envelope glycoproteins E1 and E2 were identified from the UniProt database depending on their antigenicity scores. Subsequently, we selected two distinctive sequences "SEDVYANTQLVLQRP" and "IMLLYPDHPTLLSYR" in both E1 and E2 glycoproteins respectively. These two sequences identified as the most potent T and B cell epitope-based peptides as they interacted with 6 and 7 HLA-I and 5 HLA-II molecules with an extremely low IC50 score that was verified by molecular docking. Moreover, the sequences possess no allergenicity and are certainly located outside the transmembrane region. In addition, the sequences exhibited 88.46% and 100.00% Conservancy, covering high population coverage of 89.49% to 94.74% and 60.51% to 88.87% respectively in endemic countries. The identified peptide SEDVYANTQLVLQRP and IMLLYPDHPTLLSYR can be utilized next for the development of peptide-based epitope vaccine contrary to CHIKV, so further documentations and experimentations like Antigen testing, Antigen production, Clinical trials are needed to prove the validity of it. Communicated by Ramaswamy H. Sarma.