Abstract

Virus pandemics have happened, are happening and will happen again. In recent decades, the rate of zoonotic viral spillover into humans has accelerated, mirroring the expansion of our global footprint and travel network, including the expansion of viral vectors and the destruction of natural spaces, bringing humans closer to wild animals. Once viral cross-species transmission to humans occurs, transmission cannot be stopped by cement walls but by developing barriers based on knowledge that can prevent or reduce the effects of any pandemic. Controlling a local transmission affecting few individuals is more efficient that confronting a community outbreak in which infections cannot be traced. Genetic detection, identification, and characterization of infectious agents using next-generation sequencing (NGS) has been proven to be a powerful tool allowing for the development of fast PCR-based molecular assays, the rapid development of vaccines based on mRNA and DNA, the identification of outbreaks, transmission dynamics and spill-over events, the detection of new variants and treatment of vaccine resistance mutations, the development of direct-acting antiviral drugs, the discovery of relevant minority variants to improve knowledge of the viral life cycle, strengths and weaknesses, the potential for becoming dominant to take appropriate preventive measures, and the discovery of new routes of viral transmission.

Highlights

  • The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV-2) has exposed the weakness of our surveillance system with regard to preventing and monitoring the emergence and spread of emerging, re-emerging or new viruses

  • This study reviews how next-generation sequencing (NGS) may be useful for dealing with viral pandemics, taking as an example the results of the application of those technologies to the study of SARS-CoV-2 quasispecies during the current coronavirus disease 2019 (COVID-19) pandemic

  • NGS application for the recently instated vaccination campaign for COVID-19 is to use high-throughput sequencing technologies for surveillance of vaccine escape mutations to adjust development of new vaccine formulations. Another key question is related to the capacity of the viral agent to generate resistance to treatments based on direct-acting antivirals, monoclonal antibodies, or convalescent plasma

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Summary

Introduction

The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has exposed the weakness of our surveillance system with regard to preventing and monitoring the emergence and spread of emerging, re-emerging or new viruses. During the current SARS-CoV-2 pandemic, NGS technologies have allowed for the development in record time (months) of highly effective vaccines based on mRNA/DNA [6], the development of qualitative and quantitative diagnostic solutions [7], and the identification of variants and relevant mutations in continuous surveillance [8], especially of variants with evidence of mutations impacting transmissibility, severity and/or immunity, known as variants of concern (VOC), and of their dominance and spread throughout the world [9]. A common trait among most of these viral agents is their strong ability to generate genetic variability through different mechanisms, as will be discussed later (see Section 4) This genetic variability can affect some phenotyping features such as tropism, antigenicity, and susceptibility to available antiviral drugs. This study reviews how NGS may be useful for dealing with viral pandemics, taking as an example the results of the application of those technologies to the study of SARS-CoV-2 quasispecies during the current coronavirus disease 2019 (COVID-19) pandemic

NGS for Confronting the Devastating Effects of a Pandemic
Zoonosis and NGS
Most human pathogenic viruses in a clock-like classification provided by Todd
NGS for Studying Genomic Viral Variability
NGS as a Diagnostic Tool
NGS for Studying the Origin of a Virus and Fighting against Fake Theories
NGS Using Random Primers (Metagenomics Sequencing)
Sequence Capture, Fragment Recovery and NGS Sequencing (Target Enrichment Sequencing)
Use of Amplicons (PCR Amplicon Sequencing)
Next-Next Generation Sequencing (NNGS) or Third Generation Long-Read Sequencing (TGS)
60 K–2 M bp
Findings
Summary
Full Text
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