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Understanding the mechanisms by which single-stranded RNA viruses regulate capsid assembly around their RNA genomes has become increasingly important for the development of both antiviral treatments and drug delivery systems. In this study, we investigate the effects of RNA-induced allostery in a single-stranded RNA virus—Levivirus bacteriophage MS2 assembly—using the computational methods of the Dynamic Flexibility Index and the Dynamic Coupling Index. We demonstrate that not only does asymmetric binding of RNA to a symmetric MS2 coat protein dimer increase the flexibility of the distant FG-loop, inducing a conformational change to an asymmetric dimer, but also RNA binding reorganizes long-distance communications, making all the other positions extremely sensitive to the fluctuation of the ordered FG-loop. Additionally, we find that a point mutation in the FG-loop, W82R, leads to the loss of this asymmetry in communications, likely being a leading cause for assembly-deficient dimers. Lastly, this dominant communication that enhances its dynamic coupling with all the distal positions is not only a property of the dimer but is also exhibited by all the observed capsid intermediates. This strong dynamic coupling allows for unidirectional signal transduction that drives the formation of the experimentally observed capsid intermediates and fully assembled capsid.
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Carbon dots for effective photodynamic inactivation of virus
The antiviral function of carbon dots (CDots) with visible light exposure was evaluated, for which the model bacteriophages MS2 as a surrogate of small RNA viruses were used. The results show clearly that the visible light-activated CDots are highly effective in diminishing the infectivity of MS2 in both low and high titer samples to the host E. coli cells, and the antiviral effects are dot concentration- and treatment time-dependent. The action of CDots apparently causes no significant damage to the structural integrity and morphology of the MS2 phage or the breakdown of the capsid proteins, but does result in the protein carbonylation (a commonly used indicator for protein oxidation) and the degradation of viral genomic RNA. Mechanistically the results may be understood in the framework of photodynamic effects that are associated with the unique excited state properties and processes of CDots. Opportunities for potentially broad applications of CDots coupled with visible/natural light in the prevention and control of viral transmission and spread are highlighted and discussed.
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- PAR ID:
- 10223897
- Date Published:
- Journal Name:
- RSC Advances
- Volume:
- 10
- Issue:
- 56
- ISSN:
- 2046-2069
- Page Range / eLocation ID:
- 33944 to 33954
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d0ra05849a
