Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis. Viral nonstructural proteins (NSPs) interact with a range of different ribosomal states and interfere with mRNA translation. Concurrent mutations on NSPs and spike proteins contribute to the epidemiological success of variants of concern (VOCs). The interactions between ribosomes and SARS-CoV-2 represent attractive targets for the development of antiviral therapeutics and vaccines. Recently approved COVID-19 mRNA vaccines also utilize the cellular machinery, to produce antigens and trigger immune responses. The design features of the mRNA vaccines are critical to efficient mRNA translation in ribosomes, and are directly related to the vaccine’s efficacy, safety, and immunogenicity. This review describes recent knowledge of how the SARS-CoV-2 virus’ genomic characteristics interfere with ribosomal function and mRNA translation. In addition, we discuss the current learning of the design features of mRNA vaccines and their impacts on translational activity in ribosomes. The understanding of ribosomal interactions with the virus and mRNA vaccines offers the foundation for antiviral therapeutic discovery and continuous mRNA vaccine optimization to lower the dose, to increase durability and/or to reduce adverse effects.
Highlights
Received: 21 November 2021SARS-CoV-2 is the causing pathogen of the COVID-19 pandemic that has resulted in more than 250 million cases and 5 million deaths [1,2,3]
We discuss the current learning of the design features of messenger RNA (mRNA) vaccines and their impacts on translational activity in ribosomes
The protein synthesis process begins with translation initiation, a highly ordered process that regulates mRNA translation, which is followed by elongation, during which a newly translated amino acid is added to Accepted: 28 December 2021
Summary
SARS-CoV-2 is the causing pathogen of the COVID-19 pandemic that has resulted in more than 250 million cases and 5 million deaths [1,2,3]. Nsp interacts with 50 UTR of SARS-CoV-2 and facilitates the translation of its own protein, resulting in viral replication and protein accumulation, and inhibiting anti-viral immune responses. Nsp is a protein comprised of 180 amino acids that targets cellular processes to inhibit translation, triggers host mRNA cleavage and decay, and down-regulates type I interferon (IFN) response [21,22,23,24]. Nsp of SARS-CoV-2 is vital for viral replication as it hampers the translation of cellular transcripts, shutting off host protein production, and has the ability to recruit the ribosome in order to efficiently translate the viral mRNA to allow the expression of viral genes [15]. A fully functional Nsp is necessary for virulence; the targeting of Nsp proteins and the Nsp1–ribosome interactions presents an attractive therapeutic opportunity for future studies [13,22,28]
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