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Literature detail

"But Mouse, You Are Not Alone": On Some Severe Acute Respiratory Syndrome Coronavirus 2 Variants Infecting Mice.

Michael J Kuiper1 Laurence O W Wilson2 Shruthi Mangalaganesh3,4 Carol Lee2 Daniel Reti2,5,6 Seshadri S Vasan4,7
Affiliations 7 institutions
  1. CSIRO Data61, Dockands, Victoria, Australia.
  2. CSIRO Transformational Bioinformatics Group, North Ryde, New South Wales, Australia.
  3. Monash University, Clayton, Victoria, Australia.
  4. CSIRO Australian Centre for Disease Preparedness, Geelong, Victoria, Australia.
  5. Centre for Population Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
  6. Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
  7. Department of Health Sciences, University of York, York, UK.
PMID 35022734 2021 ILAR J eng ppublish
PubMed DOI Browse context

Article

Publication summary

In silico predictions combined with in vitro, in vivo, and in situ observations collectively suggest that mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike protein's receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K, and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements, due to more favorable binding interactions with residues on the complementary angiotensin-converting enzyme 2 interface, are, however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice, whereas Delta and "Delta Plus" lack a similar biomolecular basis to do so. This paper identifies 11 countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay, and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.

AlphaFold animal reservoir COVID-19 in silico in vitro in vivo mouse adaptation SARS-CoV-2 variants COVID-19 Severe acute respiratory syndrome-related coronavirus Animals Humans Mice Mutation Peptidyl-Dipeptidase A SARS-CoV-2 Spike Glycoprotein, Coronavirus

Structured evidence records

Evidence records

4 total
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.80
Key finding

In vitro and in vivo experiments indicate that SARS-CoV-2 variants Alpha, Beta, Gamma, and Omicron can infect mice, mediated by spike mutations at positions 501 or 498.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

In silico predictions combined with in vitro, in vivo, and in situ observations collectively suggest that mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 ... Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice.

Method
in vitro assay; in vivo experiment
Experimental system
in vitro and in vivo
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Specific mutations in the SARS-CoV-2 spike receptor-binding domain enhance binding to mouse ACE2, facilitating molecular adaptation for mouse infection.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

Mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 of the spike protein's receptor binding domain; this effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K, and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements, due to more favorable binding interactions with residues on the complementary angiotensin-converting enzyme 2 interface.

Genes or proteins
spike protein
Receptors
angiotensin-converting enzyme 2
Mutations
N501 aromatic substitution; Q498 aromatic substitution; K417N; E484K; Q493K; Q493R; F486L; P499T
Mechanism types
receptor_binding; host_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.90
Key finding

Aromatic substitutions at spike RBD positions 501 or 498 enhance SARS-CoV-2 binding to the mouse ACE2 receptor, enabling receptor-mediated adaptation of certain variants to mice.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

In silico predictions combined with in vitro, in vivo, and in situ observations collectively suggest that mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 of the spike protein's receptor binding domain... Such enhancements, due to more favorable binding interactions with residues on the complementary angiotensin-converting enzyme 2 interface, are... unlikely to sustain mouse infectivity on their own.

Method
in silico; in vitro; in vivo; in situ
Receptors
angiotensin-converting enzyme 2
Zoonotic Surveillance 1 records
Zoonotic Surveillance Extraction confidence 0.80
Key finding

Targeted field surveillance of mice is recommended in multiple countries due to potential contact with humans infected with SARS-CoV-2 variants carrying adaptive mutations.

Virus
SARS-CoV-2
Location
Brazil Brazil
Supporting text

This paper identifies 11 countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay, and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s).

Geographic raw
Brazil
Country inferred
Brazil