Conserved Targets to Prevent Emerging Coronaviruses.

Fernanda Gonzalez Lomeli,Nicole Elmaraghy,Anthony Castro,Claudia V Osuna Guerrero,Laura L Newcomb

doi:10.3390/v14030563

Fernanda Gonzalez Lomeli, Nicole Elmaraghy + Show 3 more

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https://doi.org/10.3390/v14030563

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Journal: Viruses	Publication Date: Mar 9, 2022
Citations: 3	License type: CC BY 4.0

Affiliation: California State University, San Bernardino

Abstract

Novel coronaviruses emerged as zoonotic outbreaks in humans in 2003 (SARS), 2012 (MERS), and notably in 2019 (SARS2), which resulted in the COVID-19 pandemic, causing worldwide health and economic disaster. Vaccines provide the best protection against disease but cannot be developed and engineered quickly enough to prevent emerging viruses, zoonotic outbreaks, and pandemics. Antivirals are the best first line of therapeutic defense against novel emerging viruses. Coronaviruses are plus sense, single stranded, RNA genome viruses that undergo frequent genetic mutation and recombination, allowing for the emergence of novel coronavirus strains and variants. The molecular life cycle of the coronavirus family offers many conserved activities to be exploited as targets for antivirals. Here, we review the molecular life cycle of coronaviruses and consider antiviral therapies, approved and under development, that target the conserved activities of coronaviruses. To identify additional targets to inhibit emerging coronaviruses, we carried out in silico sequence and structure analysis of coronavirus proteins isolated from bat and human hosts. We highlight conserved and accessible viral protein domains and residues as possible targets for the development of viral inhibitors. Devising multiple antiviral therapies that target conserved viral features to be used in combination is the best first line of therapeutic defense to prevent emerging viruses from developing into outbreaks and pandemics.

Highlights

Academic Editor: Meehyein KimCoronaviruses are ubiquitous in bats, and spillover events into humans occurred in 2003 with SARS, again in 2012 with MERS, and most recently in 2019 with SARS-CoV-2.The initial coronavirus outbreaks were warnings for the COVID-19 pandemic, which to date has claimed over 5.97 million lives worldwide and over 954,500 in the United States [1]
Emerging viruses are a threat to human health and the global economy, as illuminated by the current global COVID-19 pandemic caused by SARSCoV-2
The molecular mechanisms vary, both viruses contain RNA genomes that change quickly during replication, including frequent mutation, which can result in antigenic drift and either reassortment of the influenza RNA genome segments or recombination of the large single RNA genome of coronaviruses, leading to antigenic shift

Summary

Introduction

Academic Editor: Meehyein KimCoronaviruses are ubiquitous in bats, and spillover events into humans occurred in 2003 with SARS, again in 2012 with MERS, and most recently in 2019 with SARS-CoV-2.The initial coronavirus outbreaks were warnings for the COVID-19 pandemic, which to date has claimed over 5.97 million lives worldwide and over 954,500 in the United States (as of 2 March 2022) [1]. Coronaviruses are ubiquitous in bats, and spillover events into humans occurred in 2003 with SARS, again in 2012 with MERS, and most recently in 2019 with SARS-CoV-2. We may see SARS-CoV-2 become endemic and require yearly vaccination updates, much like human influenza [2]. Similar to the influenza virus, given the nature of coronaviruses, novel human coronaviruses are likely to emerge again in the future. Vaccination provides excellent protection against targeted influenza A and B circulating strains, but there are years where the circulating influenza viruses change too much, and the vaccine protection loses efficacy. As reported by the CDC, influenza vaccine efficacy over the past decade ranged from a high of 60% to a low of 19% [3].

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