Feral American mink Neogale vison continues to expand its European range: time to harmonise population monitoring and coordinate control

The American mink Neogale vison is an invasive alien species in Europe that threatens endemic biodiversity and can transmit zoonotic diseases, including the SARS-CoV-2 virus. The last attempt to map the geographic range of this species in Europe, at continental scale, dates back to 2007. We aimed to update the distribution map of the feral American mink and assess its temporal trends. The information we collected was critically analysed with the aim of improving future monitoring protocols and data collection. We gathered and standardised data from 34 databases, covering 32 countries. Through 3 five-year periods from 2007 to 2021, changes in range size, hunting bags and capture statistics were analysed. We also reviewed the current situation of mink farming in the different European countries and recorded population control schemes. The American mink is now widespread in the Baltic States, France, Germany, Iceland, Ireland, Poland, Scandinavia, Spain and the UK. The species is reported to be absent in some areas (e.g. parts of the UK, Iceland and Norway). Data are deficient for several countries, mainly in south-eastern Europe. These findings indicate that, during the last 15 years, the species has continued to spread across the continent, increasing its potential extent of occurrence in most countries. Our effort to collect and harmonise data across international borders highlighted information gaps and heterogeneity in data quality. Updated distribution data on the species provided here will aid risk assessment and risk management policies. These actions require a coordinated effort for population monitoring at continental level. Monitoring effort and data collection should be intensified in south-eastern Europe to improve data on the current distribution of this invasive species. © 2023 The Authors. Mammal Review published by Mammal Society and John Wiley & Sons Ltd.

Highly conserved binding region of ACE2 as a receptor for SARS-CoV-2 between humans and mammals.

Several cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection transmitted from human owners to their dogs have recently been reported. The first ever case of SARS-CoV-2 transmission from a human owner to a domestic cat was confirmed on March 27, 2020. A tiger from a zoo in New York, USA, was also reportedly infected with SARS-CoV-2. It is believed that SARS-CoV-2 was transmitted to tigers from their caretakers, who were previously infected with this virus. On May 25, 2020, the Dutch Minister of Agriculture, Nature and Food Quality reported that two employees were infected with SARS-CoV-2 transmitted from minks. These reports have influenced us to perform a comparative analysis among angiotensin-converting enzyme 2 (ACE2) homologous proteins for verifying the conservation of specific protein regions. One of the most conserved peptides is represented by the peptide "353-KGDFR-357 (H. sapiens ACE2 residue numbering), which is located on the surface of the ACE2 molecule and participates in the binding of SARS-CoV-2 spike receptor binding domain (RBD). Multiple sequence alignments of the ACE2 proteins by ClustalW, whereas the three-dimensional structure of its binding region for the spike glycoprotein of SARS-CoV-2 was assessed by means of Spanner, a structural homology modeling pipeline method. In addition, evolutionary phylogenetic tree analysis by ETE3 was used. ACE2 works as a receptor for the SARS-CoV-2 spike glycoprotein between humans, dogs, cats, tigers, minks, and other animals, except for snakes. The three-dimensional structure of the KGDFR hosting protein region involved in direct interactions with SARS-CoV-2 spike RBD of the mink ACE2 appears to form a loop structurally related to the human ACE2 corresponding protein loop, despite of the reduced available protein length (401 residues of the mink ACE2 available sequence vs 805 residues of the human ACE2). The multiple sequence alignments of the ACE2 proteins shows high homology and complete conservation of the five amino acid residues: 353-KGDFR-357 with humans, dogs, cats, tigers, minks, and other animals, except for snakes. Where the information revealed from our examinations can support precision vaccine design and the discovery of antiviral therapeutics, which will accelerate the development of medical countermeasures, the World Health Organization recently reported on the possible risks of reciprocal infections regarding SARS-CoV-2 transmission from animals to humans.

Cryptic SARS-CoV-2 lineage identified on two mink farms as a possible result of long-term undetected circulation in an unknown animal reservoir, Poland, November 2022 to January 2023.

In late 2022 and early 2023, SARS-CoV-2 infections were detected on three mink farms in Poland situated within a few km from each other. Whole-genome sequencing of the viruses on two of the farms showed that they were related to a virus identified in humans in the same region 2 years before (B.1.1.307 lineage). Many mutations were found, including in the S protein typical of adaptations to the mink host. The origin of the virus remains to be determined.

SARS-CoV-2 in animals used for fur farming: GLEWS+ risk assessment (20 January 2021)

SARS-CoV-2 was first identified in humans in December 2019 and has since affected almost 68 million people causing over 1.5 million deaths worldwide. Animal-to-human and animal-to-animal transmission has been documented within farmed minks in several countries. SARS-CoV-2 has been identified in a farmed mink population in a number of countries. Some of the affected farms reported also workers SARS-CoV-2 infection and it is hypothesized that the mink farms were infected through human-mink transmission proving SARS-CoV-2 capability of reverse zoonosis. This Tripartite Risk Assessment, as a joint effort under the GLEWS+ initiative, completed with the Food and Agriculture Organization (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (OIE), evaluates the risk of introduction and spread of SARS-CoV-2 within fur farming systems as well as whether farmed fur animals could play a significant role in the spread of SARS-CoV-2 to humans via spillover. Additionally, using a One Health approach, the Tripartite evaluated the risk of the escaped minks leading to the establishment of a viral reservoir in susceptible wildlife populations. This work provides guidance to Members on this newly emerging threat.

Surveillance and control of SARS-CoV-2 in mustelids: An evolutionary perspective.

The relevance of mustelids in SARS-CoV-2 transmission has become increasingly evident. Alongside experimental demonstration of airborne transmission among ferrets, the major animal model for human respiratory diseases, transmission of SARS-CoV-2 within- and/or between-commercial mink farms has occurred and continues to occur. The number of mink reared for the luxury fur trade is approximately 60.5 million, across 36 mustelid-farming countries. By July 2021, SARS-CoV-2 outbreaks have been reported in 12 of these countries, at 412 European and 20 North American mink farms. Reverse zoonotic transmission events (from humans to mink) have introduced the virus to farms with subsequent extensive mink-to-mink transmission as well as further zoonotic (mink-to-human) transmission events generating cases among both farm workers and the broader community. Overcrowded housing conditions inherent within intensive mink farms, often combined with poor sanitation and welfare, both guarantee spread of SARS-CoV-2 and facilitate opportunities for viral variants, thereby effectively representing biotic hubs for viral transmission and evolution of virulence. Adequate preventative, surveillance and control measures within the mink industry are imperative both for the control of the current global pandemic and to mitigate against future outbreaks.

Pathology of animal models of COVID-19

This paper describes the pathogenesis and immunology of Macaca mulatta, Macaca fascicularis, ferrets, Syrian golden hamsters (Mesocricetus auratus), mice, cats, mink, pigs and rabbits used as models for SARS-CoV-2 infection.

SARS-CoV-2 in animals: susceptibility of animal species, risk for animal and public health, monitoring, prevention and control.

The epidemiological situation of SARS-CoV-2 in humans and animals is continually evolving. To date, animal species known to transmit SARS-CoV-2 are American mink, raccoon dog, cat, ferret, hamster, house mouse, Egyptian fruit bat, deer mouse and white-tailed deer. Among farmed animals, American mink have the highest likelihood to become infected from humans or animals and further transmit SARS-CoV-2. In the EU, 44 outbreaks were reported in 2021 in mink farms in seven MSs, while only six in 2022 in two MSs, thus representing a decreasing trend. The introduction of SARS-CoV-2 into mink farms is usually via infected humans; this can be controlled by systematically testing people entering farms and adequate biosecurity. The current most appropriate monitoring approach for mink is the outbreak confirmation based on suspicion, testing dead or clinically sick animals in case of increased mortality or positive farm personnel and the genomic surveillance of virus variants. The genomic analysis of SARS-CoV-2 showed mink-specific clusters with a potential to spill back into the human population. Among companion animals, cats, ferrets and hamsters are those at highest risk of SARS-CoV-2 infection, which most likely originates from an infected human, and which has no or very low impact on virus circulation in the human population. Among wild animals (including zoo animals), mostly carnivores, great apes and white-tailed deer have been reported to be naturally infected by SARS-CoV-2. In the EU, no cases of infected wildlife have been reported so far. Proper disposal of human waste is advised to reduce the risks of spill-over of SARS-CoV-2 to wildlife. Furthermore, contact with wildlife, especially if sick or dead, should be minimised. No specific monitoring for wildlife is recommended apart from testing hunter-harvested animals with clinical signs or found-dead. Bats should be monitored as a natural host of many coronaviruses.

SARS-CoV-2 Monitoring on Mink Farms in Poland.

Introduction: Many countries have reported severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infections in mink, and transmission back to humans has raised the concern of novel variants emerging in these animals. The monitoring system on Polish mink farms detected SARS-CoV-2 infection first in January 2021 and has been kept in place since then. Material and Methods: Oral swab samples collected between February 2021 and March 2022 from 11,853 mink from 594 farms in different regions of Poland were screened molecularly for SARS-CoV-2. Isolates from those with the highest loads of viral genetic material from positive farms were sequenced and phylogenetically analysed. Serological studies were also carried out for one positive farm in order to follow the antibody response after infection. Results: SARS-CoV-2 RNA was detected in mink on 11 farms in 8 out of 16 Polish administrative regions. Whole genome sequences were obtained for 19 SARS-CoV-2 strains from 10 out of 11 positive farms. These genomes belonged to four different variants of concern (VOC) - VOC-Gamma (20B), VOC-Delta (21J), VOC-Alpha (20I) and VOC-Omicron (21L) - and seven different Pango lineages - B.1.1.464, B.1.1.7, AY.43, AY.122, AY.126, B.1.617.2 and BA.2. One of the nucleotide and amino acid mutations specific for persistent strains found in the analysed samples was the Y453F host adaptation mutation. Serological testing of blood samples revealed a high rate of seroprevalence on the single mink farm studied. Conclusion: Farmed mink are highly susceptible to infection with SARS-CoV-2 of different lineages, including Omicron BA.2 VOC. As these infections were asymptomatic, mink may become an unnoticeable virus reservoir generating new variants potentially threatening human health. Therefore, real-time monitoring of mink is extremely important in the context of the One Health approach.

Evolutionary rate of SARS-CoV-2 increases during zoonotic infection of farmed mink.

To investigate genetic signatures of adaptation to the mink host, we characterised the evolutionary rate heterogeneity in mink-associated severe acute respiratory syndrome coronaviruses (SARS-CoV-2). In 2020, the first detected anthropozoonotic spillover event of SARS-CoV-2 occurred in mink farms throughout Europe and North America. Both spill-back of mink-associated lineages into the human population and the spread into the surrounding wildlife were reported, highlighting the potential formation of a zoonotic reservoir. Our findings suggest that the evolutionary rate of SARS-CoV-2 underwent an episodic increase upon introduction into the mink host before returning to the normal range observed in humans. Furthermore, SARS-CoV-2 lineages could have circulated in the mink population for a month before detection, and during this period, evolutionary rate estimates were between 3 × 10-3 and 1.05 × 10-2 (95 per cent HPD, with a mean rate of 6.59 × 10-3) a four- to thirteen-fold increase compared to that in humans. As there is evidence for unique mutational patterns within mink-associated lineages, we explored the emergence of four mink-specific Spike protein amino acid substitutions Y453F, S1147L, F486L, and Q314K. We found that mutation Y453F emerged early in multiple mink outbreaks and that mutations F486L and Q314K may co-occur. We suggest that SARS-CoV-2 undergoes a brief, but considerable, increase in evolutionary rate in response to greater selective pressures during species jumps, which may lead to the occurrence of mink-specific mutations. These findings emphasise the necessity of ongoing surveillance of zoonotic SARS-CoV-2 infections in the future.

One Health Investigation of SARS-CoV-2 in People and Animals on Multiple Mink Farms in Utah.

From July−November 2020, mink (Neogale vison) on 12 Utah farms experienced an increase in mortality rates due to confirmed SARS-CoV-2 infection. We conducted epidemiologic investigations on six farms to identify the source of virus introduction, track cross-species transmission, and assess viral evolution. Interviews were conducted and specimens were collected from persons living or working on participating farms and from multiple animal species. Swabs and sera were tested by SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and serological assays, respectively. Whole genome sequencing was attempted for specimens with cycle threshold values <30. Evidence of SARS-CoV-2 infection was detected by rRT-PCR or serology in ≥1 person, farmed mink, dog, and/or feral cat on each farm. Sequence analysis showed high similarity between mink and human sequences on corresponding farms. On farms sampled at multiple time points, mink tested rRT-PCR positive up to 16 weeks post-onset of increased mortality. Workers likely introduced SARS-CoV-2 to mink, and mink transmitted SARS-CoV-2 to other animal species; mink-to-human transmission was not identified. Our findings provide critical evidence to support interventions to prevent and manage SARS-CoV-2 in people and animals on mink farms and emphasizes the importance of a One Health approach to address emerging zoonoses.

Hands off the Mink! Using Environmental Sampling for SARS-CoV-2 Surveillance in American Mink.

Throughout the COVID-19 pandemic, numerous non-human species were shown to be susceptible to natural infection by SARS-CoV-2, including farmed American mink. Once infected, American mink can transfer the virus from mink to human and mink to mink, resulting in a high rate of viral mutation. Therefore, outbreak surveillance on American mink farms is imperative for both mink and human health. Historically, disease surveillance on mink farms has consisted of a combination of mortality and live animal sampling; however, these methodologies have significant limitations. This study compared PCR testing of both deceased and live animal samples to environmental samples on an active outbreak premise, to determine the utility of environmental sampling. Environmental sampling mirrored trends in both deceased and live animal sampling in terms of percent positivity and appeared more sensitive in some low-prevalence instances. PCR CT values of environmental samples were significantly different from live animal samples' CT values and were consistently high (mean CT = 36.2), likely indicating a low amount of viral RNA in the samples. There is compelling evidence in favour of environmental sampling for the purpose of disease surveillance, specifically as an early warning tool for SARS-CoV-2; however, further work is needed to ultimately determine whether environmental samples are viable sources for molecular epidemiology investigations.

SARS-CoV-2 as a Zooanthroponotic Infection: Spillbacks, Secondary Spillovers, and Their Importance.

In the midst of a persistent pandemic of a probable zoonotic origin, one needs to constantly evaluate the interplay of SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2) with animal populations. Animals can get infected from humans, and certain species, including mink and white-tailed deer, exhibit considerable animal-to-animal transmission resulting in potential endemicity, mutation pressure, and possible secondary spillover to humans. We attempt a comprehensive review of the available data on animal species infected by SARS-CoV-2, as presented in the scientific literature and official reports of relevant organizations. We further evaluate the lessons humans should learn from mink outbreaks, white-tailed deer endemicity, zoo outbreaks, the threat for certain species conservation, the possible implication of rodents in the evolution of novel variants such as Omicron, and the potential role of pets as animal reservoirs of the virus. Finally, we outline the need for a broader approach to the pandemic and epidemics, in general, incorporating the principles of One Health and Planetary Health.

Limited permissibility of ENL-R and Mv-1-Lu mink cell lines to SARS-CoV-2.

The SARS-CoV-2 pandemic started in the end of 2019 in Wuhan, China, which highlighted the scenario of frequent cross-species transmission events. From the outbreak possibly initiated by viral spill-over into humans from an animal reservoir, now we face the human host moving globally while interacting with domesticated and peridomestic animals. The emergence of a new virus into the ecosystem leads to selecting forces and species-specific adaptations. The adaptation of SARS-CoV-2 to other animals represents a risk to controlling the dissemination of this coronavirus and the emergence of new variants. Since 2020, several mink farms in Europe and the United States have had SARS-CoV-2 outbreaks with human-mink and mink-human transmission, where the mink-selected variants possibly hold evolutionary concerning advantages. Here we investigated the permissibility of mink lung-derived cells using two cell lines, Mv-1-Lu and ENL-R, against several lineages of SARS-CoV-2, including some classified as variants of concern. The viral release rate and the infectious titers indicate that these cells support infections by different SARS-CoV-2 lineages. The viral production occurs in the first few days after infection with the low viral release by these mink cells, which is often absent for the omicron variant for lung cells. The electron microscopy reveals that during the viral replication cycle, the endomembrane system of the mink-host cell undergoes typical changes while the viral particles are produced, especially in the first days of infection. Therefore, even if limited, mink lung cells may represent a selecting source for SARS-CoV-2 variants, impacting their transmissibility and pathogenicity and making it difficult to control this new coronavirus.

Chapter 5 - Coronaviruses of wild and semidomesticated animals with the potential for zoonotic transmission

Coronaviruses are present in most animal species. Some animals may then serve as a reservoir or intermediate hosts of viruses causing mild or severe to fatal diseases in humans and other animals. Infected humans may also transmit coronaviruses, such as severe acute respiratory syndrome virus (SARS-CoV)-2, to animals, including captive endangered animal species. This chapter focuses on coronaviruses of wild and semidomesticated animals, including viruses from bats, rodents, nonhuman primates, ferrets, minks, and rabbits. The ability of coronaviruses to rapidly mutate and to exchange their genetic material with other coronaviruses leads to the production of variants able to infect and adapt to new host species. Special attention is given to coronaviruses of bats and rodents since they appear to have hosted ancestral coronaviruses that indirectly lead to zoonotic transmission of highly pathogenic human viruses, including SARS-CoV, the closely related SARS-CoV-2, and Middle East respiratory syndrome virus. The RNA genomes of several bat coronaviruses, such as WIV1 and WIV16, are very similar to SARS-CoV. Coronaviruses in animals primarily cause severe disease in the respiratory, central nervous, and digestive systems but may damage other organ systems as well. Further studies on wildlife coronaviruses are advisable to avoid human epidemics or pandemics as well as to protect endangered animal species.

GPS Tracking of Free-Roaming Cats (Felis catus) on SARS-CoV-2-Infected Mink Farms in Utah.

Zoonotic transmission of SARS-CoV-2 from infected humans to other animals has been documented around the world, most notably in mink farming operations in Europe and the United States. Outbreaks of SARS-CoV-2 on Utah mink farms began in late July 2020 and resulted in high mink mortality. An investigation of these outbreaks revealed active and past SARS-CoV-2 infections in free-roaming and in feral cats living on or near several mink farms. Cats were captured using live traps, were sampled, fitted with GPS collars, and released on the farms. GPS tracking of these cats show they made frequent visits to mink sheds, moved freely around the affected farms, and visited surrounding residential properties and neighborhoods on multiple occasions, making them potential low risk vectors of additional SARS-CoV-2 spread in local communities.

SARS-CoV-2 infections in farmed minks (Neovision vision) - current data on the disease, epidemiology and emerging threat for humans and other animals

SARS-CoV-2, the betacoronavirus that causes COVID-19, has spread rapidly around the world since December 2019. It was suspected from the beginning that the primary outbreak in China, was of a zoonotic origin, but the SARS- CoV-2 animal reservoir(s) has not been definitively identified yet. So far, it has been confirmed that numerous animal species are susceptible to infection and that experimentally infected cats, shrews, hamsters and ferrets can also shed the virus. The SARS-CoV-2 was also detected in farmed mink (Neovison vison), in which it caused both, the clinical and subclinical disease, with respiratory symptoms and increased mortality. In April 2020, the first SARS-CoV-2 cases were detected in minks in the Netherlands, and to date (November 2020), further outbreaks have been confirmed in Denmark, Italy, Spain, Sweden, the United States, Greece, France and Poland. It has also been shown that the transmission of infection from humans to minks and from minks to humans may occur. The OIE is working on the inclusion of mink in the WAHIS database and encouraging the Members to provide appropriate data for this species to improve the monitoring of the epidemiological situation worldwide and prevent the establishment of a possible new reservoir for SARS-CoV-2.

Cryobanking European Mink (Mustela lutreola) Mesenchymal Stem Cells and Oocytes.

The European mink (Mustela lutreola) is one of Europe's most endangered species, and it is on the brink of extinction in the Iberian Peninsula. The species' precarious situation requires the application of new ex situ conservation methodologies that complement the existing ex situ and in situ conservation measures. Here, we report for the first time the establishment of a biobank for European mink mesenchymal stem cells (emMSC) and oocytes from specimens found dead in the Iberian Peninsula, either free or in captivity. New emMSC lines were isolated from different tissues: bone marrow (emBM-MSC), oral mucosa (emOM-MSc), dermal skin (emDS-MSC), oviduct (emO-MSc), endometrium (emE-MSC), testicular (emT-MSC), and adipose tissue from two different adipose depots: subcutaneous (emSCA-MSC) and ovarian (emOA-MSC). All eight emMSC lines showed plastic adhesion, a detectable expression of characteristic markers of MSCs, and, when cultured under osteogenic and adipogenic conditions, differentiation capacity to these lineages. Additionally, we were able to keep 227 Cumulus-oocyte complexes (COCs) in the biobank, 97 of which are grade I or II. The European mink MSC and oocyte biobank will allow for the conservation of the species' genetic variability, the application of assisted reproduction techniques, and the development of in vitro models for studying the molecular mechanisms of infectious diseases that threaten the species' precarious situation.

Role of spike compensatory mutations in the interspecies transmission of SARS-CoV-2.

SARS-CoV-2, the virus responsible for COVID-19 in humans, can efficiently infect a large number of animal species. Like any virus, and particularly RNA viruses, SARS-CoV-2 undergoes mutations during its life cycle some of which bring a selective advantage, leading to the selection of a given lineage. Minks are very susceptible to SARS-CoV-2 and owing to their presence in mass rearing, they make a good model for studying the relative importance of mutations in viral adaptation to host species. Variants, such as the mink-selected SARS-CoV-2 Y453F and D614G or H69del/V70del, Y453F, I692V and M1229I were identified in humans after spreading through densely caged minks. However, not all mink-specific mutations are conserved when the virus infects human populations back. Many questions remain regarding the interspecies evolution of SARS-CoV-2 and the dynamics of transmission leading to the emergence of new variant strains. We compared the human and mink ACE2 receptor structures and their interactions with SARS-CVoV-2 variants. In minks, ACE2 presents a Y34 amino acid instead of the H34 amino acid found in the human ACE2. H34 is essential for the interaction with the Y453 residue of the SARS-CoV-2 Spike protein. The Y453F mink mutation abolishes this conflict. A series of 18 mutations not involved in the direct ACE2 interaction was observed in addition to the Y453F and D614G in 16 different SARS-CoV-2 strains following bidirectional infections between humans and minks. These mutations were not random and were distributed into five different functional groups having an effect on the kinetics of ACE2-RD interaction. The interspecies transmission of SARS-CoV-2 from humans to minks and back to humans, generated specific mutations in each species which improved the affinity for the ACE2 receptor either by direct mutation of the core 453 residue or by associated compensatory mutations.

Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a broad range of hosts. Mink-derived SARS-CoV-2 can transmit back to humans. There is an urgent need to understand the binding mechanism of mink-derived SARS-CoV-2 variants to mink receptor. In this study, we identified all mutations in the receptor-binding domain (RBD) of spike (S) protein from mink-derived SARS-CoV-2, and we demonstrated the enhanced binding affinity of mink angiotensin-converting enzyme 2 (ACE2) to most of the mink-derived RBD variants as well as important human-originating RBD variants. Cryo-electron microscopy structures revealed that the Y453F and F486L mutations enhanced the binding forces in the interaction interface. In addition, Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and the SARS-CoV-2 pseudoviruses with Y453F, F486L, or N501T mutations were neutralized by human vaccinated sera. Therefore, our results provide valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2.

Genome Similarities between Human-Derived and Mink-Derived SARS-CoV-2 Make Mink a Potential Reservoir of the Virus.

SARS-CoV-2 has RNA as the genome, which makes the virus more prone to mutations. Occasionally, mutations help a virus to cross the species barrier. SARS-CoV-2 infections in humans and minks (Neovison vison) are examples of zoonotic spillover. Many studies on the mutational analysis of human-derived SARS-CoV-2 have been published, but insight into the mink-derived SARS-CoV-2 genome of mutations is still required. Here, we performed a mutation analysis of the mink-derived SARS-CoV-2 genome sequences. We analyzed all available full-length mink-derived SARS-CoV-2 genome sequences on GISAID (214 genome sequences from the Netherlands and 133 genome sequences from Denmark). We found a striking resemblance between human-derived and mink-derived SARS-CoV-2. Our study showed that mutation patterns in the SARS-CoV-2 genome samples from the Netherlands and Denmark were different. Out of the 201 mutations we found, only 13 mutations were shared by the Netherlands' and Denmark's mink-derived samples. We found that six mutations were prevalent in the mink-derived SARS-CoV-2 genomes, and these six mutations are also known to be prevalent in human-derived SARS-CoV-2 variants. Our study reveals that the G27948T mutation in SARS-CoV-2 leads to truncation of ORF8, which was also reported in human-derived SARS-CoV-2, thus indicating that the virus can replicate without the full-length ORF8. These resemblances between mink-derived and human-derived SARS-CoV-2 enable the virus to cross the species barrier and suggest mink a potential reservoir for the virus.