4.4 Article

Programmed-1 Ribosomal Frameshifting in coronaviruses: A therapeutic target

Journal

VIROLOGY
Volume 554, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2020.12.010

Keywords

Virus; Coronavirus; SARS-CoV; SARS-CoV-2; Covid-19; Frameshifting; Ribosome; Antiviral; Vaccine; Therapeutics

Categories

Funding

  1. Defense Threat Reduction Agency [HDTRA1-13-1-0005]
  2. University of Maryland Coronavirus Research Program Seed Grant
  3. Canadian Institutes of Health Research [OV3-170709]
  4. NIH [2T32AI051967-06A1]

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Human population growth, climate change, and globalization are fueling the emergence of novel pathogenic viruses, posing serious threats to humanity. Research into -1 ribosomal frameshift in coronaviruses has revealed its virological importance and therapeutic potential.
Human population growth, climate change, and globalization are accelerating the emergence of novel pathogenic viruses. In the past two decades alone, three such members of the coronavirus family have posed serious threats, spurring intense efforts to understand their biology as a way to identify targetable vulnerabilities. Coronaviruses use a programmed -1 ribosomal frameshift (-1 PRF) mechanism to direct synthesis of their replicase proteins. This is a critical switch in their replication program that can be therapeutically targeted. Here, we discuss how nearly half a century of research into -1 PRF have provided insight into the virological importance of -1 PRF, the molecular mechanisms that drive it, and approaches that can be used to manipulate it towards therapeutic outcomes with particular emphasis on SARS-CoV-2.

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