Possible host-adaptation of SARS-CoV-2 due to improved ACE2 receptor binding in mink.
Matthijs R A Welkers1
Alvin X Han1
Chantal B E M Reusken2
Dirk Eggink1
Affiliations2 institutions
Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Centers, location AMC, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on mink farms are increasingly observed in several countries, leading to the massive culling of animals on affected farms. Recent studies showed multiple (anthropo)zoonotic transmission events between humans and mink on these farms. Mink-derived SARS-CoV-2 sequences from The Netherlands and Denmark contain multiple substitutions in the S protein receptor binding domain (RBD). Molecular modeling showed that these substitutions increase the mean binding energy, suggestive of potential adaptation of the SARS-CoV-2 S protein to the mink angiotensin-converting enzyme 2 (ACE2) receptor. These substitutions could possibly also impact human ACE2 binding affinity as well as humoral immune responses directed to the RBD region of the SARS-CoV-2 S protein in humans. We wish to highlight these observations to raise awareness and urge for the continued surveillance of mink (and other animal)-related infections.
Recent studies showed multiple (anthropo)zoonotic transmission events between humans and mink on these farms.
Study design
outbreak investigation
Transmission direction
animal-to-human
Geographic raw
The Netherlands and Denmark
Genomic Evolution1 records
Genomic EvolutionExtraction confidence 0.80
Key finding
Genomic analysis of mink-derived SARS-CoV-2 sequences identified multiple S protein RBD substitutions associated with increased binding to mink ACE2, suggesting evolutionary adaptation to the mink host.
Mink-derived SARS-CoV-2 sequences from The Netherlands and Denmark contain multiple substitutions in the S protein receptor binding domain (RBD). Molecular modeling showed that these substitutions increase the mean binding energy, suggestive of potential adaptation of the SARS-CoV-2 S protein to the mink angiotensin-converting enzyme 2 (ACE2) receptor.
Genes or proteins
S protein; RBD
Analysis methods
sequence analysis; molecular modeling
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.95
Key finding
Substitutions in the SARS-CoV-2 spike protein RBD from mink isolates increase ACE2 binding affinity, indicating adaptation to the mink receptor.
Mink-derived SARS-CoV-2 sequences from The Netherlands and Denmark contain multiple substitutions in the S protein receptor binding domain (RBD). Molecular modeling showed that these substitutions increase the mean binding energy, suggestive of potential adaptation of the SARS-CoV-2 S protein to the mink angiotensin-converting enzyme 2 (ACE2) receptor.
Genes or proteins
S protein; receptor binding domain; RBD
Receptors
ACE2
Mechanism types
receptor_binding; host_adaptation
Receptor Usage1 records
Receptor UsageExtraction confidence 0.85
Key finding
Substitutions in the SARS-CoV-2 spike receptor binding domain enhance binding to mink ACE2 receptor, indicating potential host-specific adaptation.
Molecular modeling showed that these substitutions increase the mean binding energy, suggestive of potential adaptation of the SARS-CoV-2 S protein to the mink angiotensin-converting enzyme 2 (ACE2) receptor.
Method
molecular modeling
Receptors
ACE2
Zoonotic Surveillance1 records
Zoonotic SurveillanceExtraction confidence 0.75
Key finding
Increasing SARS-CoV-2 infections are observed on mink farms, and continued surveillance of mink-related infections is urged.
SARS-CoV-2 infections on mink farms are increasingly observed in several countries, leading to the massive culling of animals on affected farms... We wish to highlight these observations to raise awareness and urge for the continued surveillance of mink (and other animal)-related infections.
Geographic raw
The Netherlands
Country inferred
Netherlands
Citation context
References
15 references
Reference network
Force-directed citation graph. OmniVira-indexed references are prioritized and recursively expanded up to three steps.
Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine.
