Publications by authors named "Sreejith Rajasekharan"

Remodeling of the cellular endomembrane system by viruses allows for efficient and coordinated replication of the viral genome in distinct subcellular compartments termed replication organelles. As a critical step in the viral life cycle, replication organelle formation is an attractive target for therapeutic intervention, but factors central to this process are only partially understood. In this study, we corroborate that two viral proteins, nsp3 and nsp4, are the major drivers of membrane remodeling in SARS-CoV-2 infection.

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Here, we report the genome sequences of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains that were obtained from symptomatic individuals with travel histories during community surveillance in the Dominican Republic in 2020. These sequences provide a starting point for further genomic studies of gene flow and molecular diversity in the Caribbean nation. Phylogenetic analysis suggests that all genomes correspond to the B.

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Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro.

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The coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an Iraqi patient was sequenced for the first-time using Illumina MiSeq technology. There was a D614G mutation in the spike protein-coding sequence. This report is valuable for better understanding the spread of the virus in Iraq.

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There is an urgent need to identify antivirals against the coronavirus SARS-CoV-2 in the current COVID-19 pandemic and to contain future similar emergencies early on. Specific side-chain cholesterol oxidation products of the oxysterols family have been shown to inhibit a large variety of both enveloped and non-enveloped human viral pathogens. Here we report on the in vitro inhibitory activity of the redox active oxysterol 27-hydroxycholesterol against SARS-CoV-2 and against one of the common cold agents HCoV-OC43 human coronavirus without significant cytotoxicity.

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The limitations of high-throughput genomic methods used for studying virus-host interactions make it difficult to directly obtain insights on virus pathogenesis. In this chapter, the central steps of a protein structure similarity based computational approach used to predict the host interactors of Chikungunya virus are explained by highlighting the important aspects that need to be considered. Identification of such conserved set of putative interactions that allow the virus to take control of the host has the potential to deepen our understanding of the virus-specific remodeling processes of the host cell and illuminate new arenas of disease intervention.

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The rhabdovirus matrix (M) protein is a multifunctional virion protein that plays major role in virus assembly and budding, virus-induced inhibition of host gene expression and cytopathic effects observed in infected cells. The myriad roles played by this protein in the virus biology make it a critical player in viral pathogenesis. Therefore, discerning the interactions of this protein with host can greatly facilitate our understanding of virus infections, ultimately leading to both improved therapeutics and insight into cellular processes.

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The envelope proteins of Chikungunya virus (CHIKV) are known to play crucial roles in viral infection and spread. Although the role of envelope proteins in viral infection has been studied, the cellular interactors of these proteins are still elusive. In the present study, the ectodomains of CHIKV envelope proteins (E1 and E2) have been used for a high throughput yeast two-hybrid (Y2H) screening to identify the interacting host protein partners.

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Formation of virus specific replicase complex is among the most important steps that determines the fate of viral transcription and replication during Chikungunya virus (CHIKV) infection. In the present study, the authors have computationally generated a 3D structure of CHIKV late replicase complex on the basis of the interactions identified among the domains of CHIKV nonstructural proteins (nsPs) which make up the late replicase complex. The interactions among the domains of CHIKV nsPs were identified using systems such as pull down, protein interaction ELISA, and yeast two-hybrid.

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Chandipura virus (CHPV) is an arthropod borne rhabdovirus associated with acute encephalitis in children below the age of 15 years in the tropical states of India. Although the entry of the virus into the nervous system is among the crucial events in the pathogenesis of CHPV, the exact mechanism allowing CHPV to invade the central nervous system (CNS) is currently poorly understood. In the present review, based on the knowledge of host interactors previously predicted for CHPV, along with the support from experimental data available for other encephalitic viruses, the authors have speculated the various plausible modes by which CHPV could surpass the blood-brain barrier and invade the CNS to cause encephalitis whilst evading the host immune surveillance.

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The nucleocapsid (N) protein of Chandipura virus (CHPV) plays a crucial role in viral life cycle, besides being an important structural component of the virion through proper organization of its interactions with other viral proteins. In a recent study, the authors had mapped the associations among CHPV proteins and shown that N protein interacts with four of the viral proteins: N, phosphoprotein (P), matrix protein (M), and glycoprotein (G). The present study aimed to distinguish the regions of CHPV N protein responsible for its interactions with other viral proteins.

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Chandipura virus (CHPV), alike other pathogens, exploits the cellular infrastructure of their hosts through complex network of interactions for successful infection. CHPV being a recently emerged pediatric encephalitic virus, the mechanisms involved in the establishment of viral persistence are still ill defined. Because the protein interface between CHPV and its host provides one means by which the virus invades and seize control of their human host machinery, the authors in this study have employed computational methods to create a network of putative protein-protein interactions between CHPV and its human host to shed light on the hitherto less-known CHPV biology.

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