Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

PLoS Pathog. 2021 Dec 30;17(12):e1010106. doi: 10.1371/journal.ppat.1010106. eCollection 2021 Dec.


The development of safe and effective vaccines in a record time after the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a remarkable achievement, partly based on the experience gained from multiple viral outbreaks in the past decades. However, the Coronavirus Disease 2019 (COVID-19) crisis also revealed weaknesses in the global pandemic response and large gaps that remain in our knowledge of the biology of coronaviruses (CoVs) and influenza viruses, the 2 major respiratory viruses with pandemic potential. Here, we review current knowns and unknowns of influenza viruses and CoVs, and we highlight common research challenges they pose in 3 areas: the mechanisms of viral emergence and adaptation to humans, the physiological and molecular determinants of disease severity, and the development of control strategies. We outline multidisciplinary approaches and technological innovations that need to be harnessed in order to improve preparedeness to the next pandemic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents
  • COVID-19 / therapy
  • COVID-19 / transmission
  • COVID-19 / virology*
  • Drug Development
  • Evolution, Molecular
  • Humans
  • Influenza, Human / therapy
  • Influenza, Human / transmission
  • Influenza, Human / virology*
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae / physiology*
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / physiology*
  • Selection, Genetic
  • Viral Load
  • Viral Vaccines


  • Antiviral Agents
  • Viral Vaccines

Grants and funding

The french influenza research network ResaFlu coordinated by NN is funded by the Centre National de la Recherche Scientifique (CNRS GDR 2073). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.