scholarly journals Crippling life support for SARS-CoV-2 and other viruses through synthetic lethality

2020 ◽  
Vol 219 (10) ◽  
Author(s):  
Fred D. Mast ◽  
Arti T. Navare ◽  
Almer M. van der Sloot ◽  
Jasmin Coulombe-Huntington ◽  
Michael P. Rout ◽  
...  
Keyword(s):  
Life Cycle ◽  
Host Cell ◽  
Life Support ◽  
Synthetic Lethality ◽  
Viral Disease ◽  
Viral Life Cycle ◽  
Viral Spread ◽  
Global Spread ◽  
Cell Networks ◽  
Virus Factory

With the rapid global spread of SARS-CoV-2, we have become acutely aware of the inadequacies of our ability to respond to viral epidemics. Although disrupting the viral life cycle is critical for limiting viral spread and disease, it has proven challenging to develop targeted and selective therapeutics. Synthetic lethality offers a promising but largely unexploited strategy against infectious viral disease; as viruses infect cells, they abnormally alter the cell state, unwittingly exposing new vulnerabilities in the infected cell. Therefore, we propose that effective therapies can be developed to selectively target the virally reconfigured host cell networks that accompany altered cellular states to cripple the host cell that has been converted into a virus factory, thus disrupting the viral life cycle.

scholarly journals Role of Lipid Transfer Proteins (LTPs) in the Viral Life Cycle

2021 ◽  
Vol 12 ◽  
Author(s):  
Kiran Avula ◽  
Bharati Singh ◽  
Preethy V. Kumar ◽  
Gulam H. Syed
Keyword(s):  
Life Cycle ◽  
Viral Replication ◽  
Host Cell ◽  
Lipid Membrane ◽  
Positive Curvature ◽  
Viral Life Cycle ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Flexible Form ◽  
Cellular Components

Viruses are obligate parasites that depend on the host cell machinery for their replication and dissemination. Cellular lipids play a central role in multiple stages of the viral life cycle such as entry, replication, morphogenesis, and egress. Most viruses reorganize the host cell membranes for the establishment of viral replication complex. These specialized structures allow the segregation of replicating viral RNA from ribosomes and protect it from host nucleases. They also facilitate localized enrichment of cellular components required for viral replication and assembly. The specific composition of the lipid membrane governs its ability to form negative or positive curvature and possess a rigid or flexible form, which is crucial for membrane rearrangement and establishment of viral replication complexes. In this review, we highlight how different viruses manipulate host lipid transfer proteins and harness their functions to enrich different membrane compartments with specific lipids in order to facilitate multiple aspects of the viral life cycle.

Interplay between host cell and hepatitis C virus in regulating viral replication

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Johannes G. Bode ◽  
Erwin D. Brenndörfer ◽  
Juliane Karthe ◽  
Dieter Häussinger
Keyword(s):  
Life Cycle ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Cell ◽  
Growth Factor Receptor ◽  
Protein Translation ◽  
Viral Life Cycle ◽  
Cellular Growth ◽  
Viral Genomes ◽  
Associated Proteins

Abstract Viral life cycle as that of the hepatitis C virus (HCV) completely relies on host cell infrastructure, presupposing that the virus has evolved mechanisms to utilize and control all cellular molecules or pathways required for viral life cycle. Hence, HCV must have acquired the ability to gain access to key pathways controlling processes, such as cell growth, apoptosis and protein synthesis, which are all considered to also be crucial for liver regeneration. This occurs in a balanced way permitting persistent replication of viral genomes and production of infectious particles without endangering host cell viability and survival. In particular during the last decade, accumulating evidence indicates that HCV utilizes signaling pathways of the host with major impact on cellular growth, viability, cell cycle or cellular metabolism, such as epidermal growth factor-receptor mediated signals, the PI3K/Akt cascade or the family of Src kinases. Furthermore, HCV specifically interacts with parts of the cellular machinery involved in protein translation, processing, maturation and transport, such as components of the translation complex, the heat shock protein family, the immunophilins or the vesicle-associated membrane protein-associated proteins A and B. The present review focuses on the interplay between viral proteins and these factors of the host cell enabling the virus to utilize host cell infrastructure.

scholarly journals Drug Design Strategies for the Treatment of Viral Disease. Plant Phenolic Compounds and Their Derivatives

2021 ◽  
Vol 12 ◽  
Author(s):  
Monika Kowalczyk ◽  
Aleksandra Golonko ◽  
Renata Świsłocka ◽  
Monika Kalinowska ◽  
Monika Parcheta ◽  
...  
Keyword(s):  
Life Cycle ◽  
Phenolic Compounds ◽  
Drug Design ◽  
Metal Ion ◽  
Microsomal Triglyceride Transfer Protein ◽  
Viral Disease ◽  
Viral Life Cycle ◽  
Host Cells ◽  
Design Strategies ◽  
Host Membrane

The coronavirus pandemic (SARS CoV-2) that has existed for over a year, constantly forces scientists to search for drugs against this virus. In silico research and selected experimental data have shown that compounds of natural origin such as phenolic acids and flavonoids have promising antiviral potential. Phenolic compounds inhibit multiplication of viruses at various stages of the viral life cycle, e.g., attachment (disturbance of the interaction between cellular and viral receptors), penetration (inhibition of viral pseudo-particle fusion to the host membrane), replication (inhibition of integrase and 3C-like protease), assembly and maturation (inhibition of microsomal triglyceride transfer protein (MTP) activity hydrolysis) and release (inhibition of secretion of apolipoprotein B (apoB) from infected cells). Phenolic compounds also indirectly influence on the viral life cycle by affecting the host cell’s biochemical processes that viruses use for their own benefit. Phenolic compounds may inhibit the proteasomes and cellular deubiquitinating activity that causes an increase in the ubiquitinated proteins level in host cells. This, in turn, contributes to the lowering the available ubiquitin molecules that viruses could use for their own replication. One of the drug design strategy for the treatment of viral diseases may be an enhancement of the antiviral properties of phenolic compounds by metal complexation. Many studies have shown that the presence of a metal ion in the structure can significantly affect the affinity of the compound to key structural elements of the SARS CoV-2, such as Mpro protease, RNA-dependent RNA polymerase (RdRp) and spike protein. We believe that in the era of coronavirus pandemic, it is necessary to reconsider the search for therapeutics among well-known compounds of plant origin and their metal complexes.

scholarly journals Nucleosome Positioning on Episomal Human Papillomavirus DNA in Cultured Cells

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 772
Author(s):  
Isao Murakami ◽  
Takashi Iwata ◽  
Tohru Morisada ◽  
Kyoko Tanaka ◽  
Daisuke Aoki
Keyword(s):  
Life Cycle ◽  
Cultured Cells ◽  
Basal Layer ◽  
Nucleosome Positioning ◽  
Viral Life Cycle ◽  
Human Papillomaviruses ◽  
Host Cells ◽  
Micrococcal Nuclease ◽  
Hpv Dna ◽  
Dna Replication And Repair

Several human papillomaviruses (HPV) are associated with the development of cervical carcinoma. HPV DNA synthesis is increased during the differentiation of infected host keratinocytes as they migrate from the basal layer of the epithelium to the spinous layer, but the molecular mechanism is unclear. Nucleosome positioning affects various cellular processes such as DNA replication and repair by permitting the access of transcription factors to promoters to initiate transcription. In this study, nucleosome positioning on virus chromatin was investigated in normal immortalized keratinocytes (NIKS) stably transfected with HPV16 or HPV18 genomes to determine if there is an association with the viral life cycle. Micrococcal nuclease-treated DNA analyzed by Southern blotting using probes against HPV16 and HPV18 and quantified by nucleosome scanning analysis using real-time PCR revealed mononucleosomal-sized fragments of 140–200 base pairs that varied in their location within the viral genome according to whether the cells were undergoing proliferation or differentiation. Notably, changes in the regions around nucleotide 110 in proliferating and differentiating host cells were common to HPV16 and HPV18. Our findings suggest that changes in nucleosome positions on viral DNA during host cell differentiation is an important regulatory event in the viral life cycle.

scholarly journals A Comprehensive, Flexible Collection of SARS-CoV-2 Coding Regions

2020 ◽  
Vol 10 (9) ◽  
pp. 3399-3402 ◽  
Author(s):  
Dae-Kyum Kim ◽  
Jennifer J Knapp ◽  
Da Kuang ◽  
Aditya Chawla ◽  
Patricia Cassonnet ◽  
...  
Keyword(s):  
Life Cycle ◽  
Viral Life Cycle ◽  
Coding Sequences ◽  
Coding Regions ◽  
Global Pandemic ◽  
The World ◽  
Molecular Studies ◽  
Widespread Availability ◽  
Rapid Transfer

Abstract The world is facing a global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus. Here we describe a collection of codon-optimized coding sequences for SARS-CoV-2 cloned into Gateway-compatible entry vectors, which enable rapid transfer into a variety of expression and tagging vectors. The collection is freely available. We hope that widespread availability of this SARS-CoV-2 resource will enable many subsequent molecular studies to better understand the viral life cycle and how to block it.

scholarly journals Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

Viruses ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 82 ◽  
Author(s):  
Di Sun ◽  
Shun Chen ◽  
Anchun Cheng ◽  
Mingshu Wang
Keyword(s):  
Life Cycle ◽  
Viral Life Cycle ◽  
Host Cells

scholarly journals AdEasy-based cloning system to generate tropism expanded replicating adenoviruses expressing transgenes late in the viral life cycle

Gene Therapy ◽  
2005 ◽  
Vol 12 (17) ◽  
pp. 1347-1352 ◽  
Author(s):  
M Lie-A-Ling ◽  
C T Bakker ◽  
J G Wesseling ◽  
P J Bosma
Keyword(s):  
Life Cycle ◽  
Viral Life Cycle ◽  
Cloning System
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