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. 2021 Jan 4;7(1):veaa094.
doi: 10.1093/ve/veaa094. eCollection 2021 Jan.

Possible host-adaptation of SARS-CoV-2 due to improved ACE2 receptor binding in mink

Matthijs R A Welkers  1 , Alvin X Han  1 , Chantal B E M Reusken  2 , Dirk Eggink  1
Affiliations

Possible host-adaptation of SARS-CoV-2 due to improved ACE2 receptor binding in mink

Matthijs R A Welkers et al. Virus Evol. .

Abstract

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.

Keywords: SARS-CoV-2; host adaptation; humoral immunity; mink; protein structure; public health.

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Figures

Figure 1.
Figure 1.
Structure of the SARS-CoV-2 RBD bound to ACE2 and location of substitutions within the mink-derived SARS-CoV-2 RBD. (A) Overview of SARS CoV-2 spike RBD interactions with ACE2. ACE2 is shown in green and RBD in light blue. Positions of residues 453, 486, and 501 are indicated. (B) Comparisons of interactions of human derived SARS-CoV-2 RBD–ACE2 (upper panels) and mink-derived SARS-CoV RBD–ACE2 interfaces (lower panels). ACE2 is shown in green and RBD in different shades of blue. Residues 453, 486, and 501 are indicated. Substitutions within mink RBD and ACE2 are indicated in orange and yellow, respectively. Modeling of substitutions and pictures produced by PyMol (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC) on structure PDB 6MOJ (Lan et al. 2020).
See this image and copyright information in PMC

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