scholarly journals Rational pharmacological approach to clinical studies for the treatment of SARS-COV-2 infection

2020 ◽  
Vol 19 (4) ◽  
pp. 42
Author(s):  
Antônia Dailane Dos Santos Rabêlo ◽  
Gizelle Gomes De Souza ◽  
Rosilene Ribeiro De Sousa ◽  
Charllyton Luis Sena Da Costa
Keyword(s):  
Viral Particle ◽  
Scientific Information ◽  
Lessons Learned ◽  
Cell Replication ◽  
Particle Assembly ◽  
Rational Combination ◽  
Different Populations ◽  
Multiple Drugs ◽  
Molecular Components ◽  
Viral Particle Assembly

AbstractThe global emergency generated by the COVID-19 pandemic caused by the SARS-COV-2 virus has created serious impacts on the different populations of the planet and has triggered the generation of scientific information on an unprecedented scale until then for a single topic. One of the consequences of the global scientific effort lies in the large number of substances already tested, by different methods, the search for an effective treatment for the infection and the consequent disease, remaining without absolute success so far. Assimilating the lessons, learned from the successful adoption of therapies combining multiple drugs used in HIV infection, the evidence obtained from the large amount of published information regarding the action of many substances with different mechanisms, now allows the proposition, in this work, of tests clinical trials for the evaluation of regimens composed of at least three drugs in combination. Rational combination schemes can target different molecular components of the virus affecting different points in the SARS-COV-2 replication cycle, such as virus fusion to the host cell, replication and viral particle assembly generating a potentially more effective synergistic effect than attempts using a single substance.Keywords: antiviral, pandemic, combination therapy.

scholarly journals The GLN Family of Murine Endogenous Retroviruses Contains an Element Competent for Infectious Viral Particle Formation

2008 ◽  
Vol 82 (9) ◽  
pp. 4413-4419 ◽  
Author(s):  
David Ribet ◽  
Francis Harper ◽  
Cécile Esnault ◽  
Gérard Pierron ◽  
Thierry Heidmann
Keyword(s):  
Viral Particle ◽  
Leukemia Virus ◽  
Endogenous Retroviruses ◽  
Particle Assembly ◽  
New Class ◽  
Mouse Mammary Tumor ◽  
The Family ◽  
Tumor Virus ◽  
Mouse Cells ◽  
Viral Particle Assembly

ABSTRACT Several families of endogenous retroviruses (ERVs) have been identified in the mouse genome, in several instances by in silico searches, but for many of them it remains to be determined whether there are elements that can still encode functional retroviral particles. Here, we identify, within the GLN family of highly reiterated ERVs, one, and only one, copy that encodes retroviral particles prone to infection of mouse cells. We show that its envelope protein confers an ecotropic host range and recognizes a receptor different from mCAT1 and mSMIT1, the two previously identified receptors for other ecotropic mouse retroviruses. Electron microscopy disclosed viral particle assembly and budding at the cell membrane, as well as release of mature particles into the extracellular space. These particles are closely related to murine leukemia virus (MLV) particles, with which they have most probably been confused in the past. This study, therefore, identifies a new class of infectious mouse ERVs belonging to the family Gammaretroviridae, with one family member still functional today. This family is in addition to the two MLV and mouse mammary tumor virus families of active mouse ERVs with an extracellular life cycle.

scholarly journals Nanoscale Mechanisms Underlying HIV-1 Viral Particle Assembly and Release

2014 ◽  
Vol 106 (2) ◽  
pp. 5a-6a
Author(s):  
Jennifer Lippincott-Schwartz ◽  
Prabuddha Sengupta ◽  
Antony Chen ◽  
Schuyler van Engelenburg
Keyword(s):  
Viral Particle ◽  
Particle Assembly ◽  
Viral Particle Assembly ◽  
Hiv 1

scholarly journals A Proline-Rich N-Terminal Region of the Dengue Virus NS3 Is Crucial for Infectious Particle Production

2016 ◽  
Vol 90 (11) ◽  
pp. 5451-5461 ◽  
Author(s):  
Leopoldo G. Gebhard ◽  
Néstor G. Iglesias ◽  
Laura A. Byk ◽  
Claudia V. Filomatori ◽  
Federico A. De Maio ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Viral Particle ◽  
Rna Replication ◽  
Particle Formation ◽  
Human Pathogen ◽  
Particle Assembly ◽  
Infectious Particle ◽  
Viral Particles ◽  
Reporter Systems ◽  
Viral Particle Assembly

ABSTRACTDengue virus is currently the most important insect-borne viral human pathogen. Viral nonstructural protein 3 (NS3) is a key component of the viral replication machinery that performs multiple functions during viral replication and participates in antiviral evasion. Using dengue virus infectious clones and reporter systems to dissect each step of the viral life cycle, we examined the requirements of different domains of NS3 on viral particle assembly. A thorough site-directed mutagenesis study based on solvent-accessible surface areas of NS3 revealed that, in addition to being essential for RNA replication, different domains of dengue virus NS3 are critically required for production of infectious viral particles. Unexpectedly, point mutations in the protease, interdomain linker, or helicase domain were sufficient to abolish infectious particle formation without affecting translation, polyprotein processing, or RNA replication. In particular, we identified a novel proline-rich N-terminal unstructured region of NS3 that contains several amino acid residues involved in infectious particle formation. We also showed a new role for the interdomain linker of NS3 in virion assembly. In conclusion, we present a comprehensive genetic map of novel NS3 determinants for viral particle assembly. Importantly, our results provide evidence of a central role of NS3 in the coordination of both dengue virus RNA replication and particle formation.IMPORTANCEDengue virus is an important human pathogen, and its prominence is expanding globally; however, basic aspects of its biology are still unclear, hindering the development of effective therapeutic and prophylactic treatments. Little is known about the initial steps of dengue and other flavivirus particle assembly. This process involves a complex interplay between viral and cellular components, making it an attractive antiviral target. Unpredictably, we identified spatially separated regions of the large NS3 viral protein as determinants for dengue virus particle assembly. NS3 is a multifunctional enzyme that participates in different steps of the viral life cycle. Using reporter systems to dissect different viral processes, we identified a novel N-terminal unstructured region of the NS3 protein as crucial for production of viral particles. Based on our findings, we propose new ideas that include NS3 as a possible scaffold for the viral assembly process.

scholarly journals Functional Redundancy in HIV-1 Viral Particle Assembly

2012 ◽  
Vol 86 (23) ◽  
pp. 12991-12996 ◽  
Author(s):  
I. P. O'Carroll ◽  
R. M. Crist ◽  
J. Mirro ◽  
D. Harvin ◽  
F. Soheilian ◽  
...  
Keyword(s):  
Viral Particle ◽  
Functional Redundancy ◽  
Particle Assembly ◽  
Viral Particle Assembly ◽  
Hiv 1

scholarly journals HIV-1 Gag protein with or without p6 specifically dimerizes on the viral RNA packaging signal

2020 ◽  
Vol 295 (42) ◽  
pp. 14391-14401 ◽  
Author(s):  
Samantha Sarni ◽  
Banhi Biswas ◽  
Shuohui Liu ◽  
Erik D. Olson ◽  
Jonathan P. Kitzrow ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Viral Particle ◽  
Rna Binding ◽  
Packaging Signal ◽  
Independent Manner ◽  
Particle Assembly ◽  
Gag Protein ◽  
Viral Particle Assembly ◽  
Hiv 1 ◽  
Psi Rna

The HIV-1 Gag protein is responsible for genomic RNA (gRNA) packaging and immature viral particle assembly. Although the presence of gRNA in virions is required for viral infectivity, in its absence, Gag can assemble around cellular RNAs and form particles resembling gRNA-containing particles. When gRNA is expressed, it is selectively packaged despite the presence of excess host RNA, but how it is selectively packaged is not understood. Specific recognition of a gRNA packaging signal (Psi) has been proposed to stimulate the efficient nucleation of viral assembly. However, the heterogeneity of Gag–RNA interactions renders capturing this transient nucleation complex using traditional structural biology approaches challenging. Here, we used native MS to investigate RNA binding of wild-type (WT) Gag and Gag lacking the p6 domain (GagΔp6). Both proteins bind to Psi RNA primarily as dimers, but to a control RNA primarily as monomers. The dimeric complexes on Psi RNA require an intact dimer interface within Gag. GagΔp6 binds to Psi RNA with high specificity in vitro and also selectively packages gRNA in particles produced in mammalian cells. These studies provide direct support for the idea that Gag binding to Psi specifically promotes nucleation of Gag–Gag interactions at the early stages of immature viral particle assembly in a p6-independent manner.

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