References for ribosomal proteins and SARS

Ribosomal proteins as a possible tool for blocking SARS-COV 2 virus replication for a potential prospective treatment

Medical HypothesesVolume 143, October 2020, 109904
  • Covid 19 represents a threat for the humanity so there is a dire need to produce a treatment or a protocol to avoid its spread.
  • Ribosomal proteins may resemble an effective tool for attenuation of viral replication.
  • RPL9 can be over expressed and purified from bacteria, yeast and humans.
  • More clinical and cytotoxicity studies are needed to produce an effective and reliable treatment to this pandemic disease.

Coronavirus disease (COVID-19) is caused by SARS-COV2 and has resulted in more than four million cases globally and the death cases exceeded 300,000. Normally, a range of surviving and propagating host factors must be employed for the completion of the infectious process including RPs. Viral protein biosynthesis involves the interaction of numerous RPs with viral mRNA, proteins which are necessary for viruses replication regulation and infection inside the host cells. Most of these interactions are crucial for virus activation and accumulation. However, only small percentage of these proteins is specifically responsible for host cells protection by triggering the immune pathway against virus. This research proposes RPs extracted from bacillus sp. and yeast as new forum for the advancement of antiviral therapy. Hitherto, antiviral therapy with RPs-involving viral infection has not been widely investigated as critical targets. Also, exploring antiviral strategy based on RPs could be a promising guide for more potential therapeutics.




New targets for antivirals: the ribosomal A-site and the factors that interact with it

2002 Aug 15;300(1):60-70.

Many viruses use programmed -1 ribosomal frameshifting to ensure the correct ratio of viral structural to enzymatic proteins. Alteration of frameshift efficiencies changes these ratios, in turn inhibiting viral particle assembly and virus propagation. Previous studies determined that anisomycin, a peptidyl transferase inhibitor, specifically inhibited -1 frameshifting and the ability of yeast cells to propagate the L-A and M(1) dsRNA viruses (J. D. Dinman, M. J. Ruiz-Echevarria, K. Czaplinski, and S. W. Peltz, 1997, Proc. Natl. Acad. Sci. USA 94, 6606-6611). Here we show that preussin, a pyrollidine that is structurally similar to anisomycin (R. E. Schwartz, J. Liesch, O. Hensens, L. Zitano, S. Honeycutt, G. Garrity, R. A. Fromtling, J. Onishi, and R. Monaghan, 1988. J. Antibiot. (Tokyo) 41, 1774–1779), also inhibits -1 programmed ribosomal frameshifting and virus propagation by acting at the same site or through the same mechanism as anisomycin. Since anisomycin is known to assert its effect at the ribosomal A-site, we undertook a pharmacogenetic analysis of mutants of trans-acting eukaryotic elongation factors (eEFs) that function at this region of the ribosome. Among mutants of eEF1A, a correlation is observed between resistance/susceptibility profiles to preussin and anisomycin, and these in turn correlate with programmed -1 ribosomal frameshifting efficiencies and killer virus phenotypes. Among mutants of eEF2, the extent of resistance to preussin correlates with resistance to sordarin, an eEF2 inhibitor. These results suggest that structural features associated with the ribosomal A-site and with the trans-acting factors that interact with it may present a new set of molecular targets for the rational design of antiviral compounds.




Translating old drugs into new treatments: ribosomal frameshifting as a target for antiviral agents

. 1998 Apr 1; 16(4): 190–196.

Programmed ribosomal frameshifting is used by many viruses to regulate the production of structural and enzymatic proteins. Altering the frameshifting efficiencies disrupts the virus life cycle and eliminates or reduces virus production. Ribosomal frameshifting therefore provides a unique target on which antiviral agents can function. This article describes a series of rapid assay strategies that have been developed and used to identify potential antiviral agents that target programmed −1 ribosomal frameshifting.



Regulation of Ribosomal Proteins on Viral Infection


Ribosomal proteins (RPs), in conjunction with rRNA, are major components of ribosomes involved in the cellular process of protein biosynthesis, known as “translation”. The viruses, as the small infectious pathogens with limited genomes, must recruit a variety of host factors to survive and propagate, including RPs. At present, more and more information is available on the functional relationship between RPs and virus infection. This review focuses on advancements in my own understanding of critical roles of RPs in the life cycle of viruses. Various RPs interact with viral mRNA and proteins to participate in viral protein biosynthesis and regulate the replication and infection of virus in host cells. Most interactions are essential for viral translation and replication, which promote viral infection and accumulation, whereas the minority represents the defense signaling of host cells by activating immune pathway against virus. RPs provide a new platform for antiviral therapy development, however, at present, antiviral therapeutics with RPs involving in virus infection as targets is limited, and exploring antiviral strategy based on RPs will be the guides for further study.


Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation

. 2012 Dec; 86(24): 13598–13608.

Severe acute respiratory syndrome (SARS) coronavirus nonstructural protein 1 (nsp1) binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (IRES)-driven mRNAs, including SARS coronavirus mRNAs, hepatitis C virus (HCV), and cricket paralysis virus (CrPV) IRES-driven mRNAs that are resistant to nsp1-induced RNA cleavage. We used an nsp1 mutant, nsp1-CD, lacking the RNA cleavage function, to delineate the mechanism of nsp1-mediated translation inhibition and identify the translation step(s) targeted by nsp1. nsp1 and nsp1-CD had identical inhibitory effects on mRNA templates that are resistant to nsp1-induced RNA cleavage, implying the validity of using nsp1-CD to dissect the translation inhibition function of nsp1. We provide evidence for a novel mode of action of nsp1. nsp1 inhibited the translation initiation step by targeting at least two separate stages: 48S initiation complex formation and the steps involved in the formation of the 80S initiation complex from the 48S complex. nsp1 had a differential, mRNA template-dependent, inhibitory effect on 48S and 80S initiation complex formation. nsp1 inhibited different steps of translation initiation on CrPV and HCV IRES, both of which initiate translation via an IRES-40S binary complex intermediate; nsp1 inhibited binary complex formation on CrPV IRES and 48S complex formation on HCV IRES. Collectively, the data revealed that nsp1 inhibited translation by exerting its effect on multiple stages of translation initiation, depending on the mechanism of initiation operating on the mRNA template.