Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

Abstract

Severe acute respiratory coronavirus 2 (SARS-CoV-2), the agent of the ongoing COVID-19 pandemic, jumped into humans from an unknown animal reservoir in late 2019. In line with other coronaviruses, SARS-CoV-2 has the potential to infect a broad range of hosts. SARS-CoV-2 genomes have now been isolated from cats, dogs, lions, tigers and minks. SARS-CoV-2 seems to transmit particularly well in mink farms with outbreaks reported in Spain, Sweden, the Netherlands, Italy, the USA and Denmark. Genomic data from SARS-CoV-2 isolated from infected minks provides a natural case study of a secondary host jump of the virus, in this case from humans to animals, and occasionally back again. We screened published SARS-CoV-2 genomes isolated from minks for the presence of recurrent mutations common in mink but infrequent in SARS-CoV-2 genomes isolated from human infections. We identify 23 recurrent mutations including three nonsynonymous mutations in the Receptor Binding Domain of the SARS-CoV-2 spike protein that independently emerged at least four times but are only rarely observed in human lineages. The repeat emergence of mutations across phylogenetically distinct lineages of the virus isolated from minks points to ongoing adaptation of SARS-CoV-2 to a new host. The rapid acquisition and spread of SARS-CoV-2 mutations in minks suggests that if a similar phenomenon of host adaptation had occurred upon its jump into humans, those human-specific mutations would likely have reached fixation already before the first SARS-CoV-2 genomes were generated.Data SummaryAll genome assemblies considered in this manuscript are openly available on registration with GISAID (https://www.gisaid.org). Information on the included assemblies, including the accessions used in the global analysis are provided in Tables S1-S2.

Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice

“…3E). We found no reductions in SARS-2 RBD binding as a result of mutations (Y453F, the “Danish mink variant” ( 45 ) or a Q493K/Q498Y/P499T triple mutant ( 46 )) (fig. S3C), no binding of any elicited sera to MERS-CoV RBD (fig.…”

“…(A,B) Binding of serum IgGs to (A) Rs4081 and (B) RaTG13 RBDs. (C) Binding of serum IgGs to SARS-2 RBD (left), a triple RBD mutant in a mouse-adapted SARS-CoV-2 ( 46 ) that includes substitutions adjacent to the N501Y RBD mutation in an emergent UK SARS-CoV-2 lineage (https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563) (middle), and Y453F, the “Danish mink variant” ( 45 ) (right). (D) Binding of serum IgGs to RBD from MERS-CoV (a non-ACE2-binding merbecovirus, representing a different subgenus from sarbecoviruses).…”

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines

“…A double deletion of amino acids H69-V70 in the N-terminal domain (NTD) of Spike often co-occurs with one of 3 mutations in RBD: N501Y, N439K, or Y453F (27). Y453F is associated with a mink farm outbreak in Denmark, with and without the presence of a ΔH69/V70 deletion (27, 28), but is also found in people in Denmark and the UK ( Figure 1 ). N439K mutation usually occurs with ΔH69/V70 but occurs frequently without the ΔH69/V70 mutation as well.…”

CovRadar: Continuously tracking and filtering SARS-CoV-2 mutations for molecular surveillance

“…One of the most significant zoonotic events to date is the host jump between mink and humans. Several mutations are currently under discussion whether they are related to mink and what significance they have for the soon-tobe-released vaccines (van Dorp et al, 2020). Using CovRadar, we looked at the positions in the available Danish mink data with high allele frequencies and compared them with the human data before and after the mink outbreak.…”