Experimental Infection of Mink with SARS-COV-2 Omicron Variant and Subsequent Clinical Disease

Virtanen, Jenni; Aaltonen, Kirsi; Kegler, Kristel; Venkat, Vinaya; Niamsap, Thanakorn; Kareinen, Lauri; Malmgren, Rasmus; Kivelä, Olga; Atanasova, Nina S.; Österlund, Pamela; Smura, Teemu; Sukura, Antti; Strandin, Tomas; Dutra, Lara; Vapalahti, Olli; Nordgren, Heli; Kant, Ravi; Sironen, Tarja

doi:10.3201/eid2806.220328

Cited by 13 publications

(8 citation statements)

References 9 publications

(10 reference statements)

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“…Our structural findings are supported by numerous studies that discovered the same mouse-specific mutations Q493R (or a similar Q493K) and Q498R ( 32 – 38 ). It is worth noting that although the prototypic SARS-CoV-2 does not infect mice efficiently, some of the earlier SARS-CoV-2 variants from humans and other animal species had evolved the N501Y mutation that can facilitate SARS-CoV-2’s usage of mACE2 as its receptor ( 20 , 39 , 40 ). Indeed, as the current study has demonstrated, the N501Y mutation is structurally adapted to ACE2 from more than one host species.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant

Zhang

Shi

Geng

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The sudden emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant has raised questions about its animal reservoir. Here, we investigated receptor recognition of the omicron’s receptor-binding domain (RBD), focusing on four of its mutations (Q493R, Q498R, N501Y, and Y505H) surrounding two mutational hotspots. These mutations have variable effects on the RBD’s affinity for human angiotensin-converting enzyme 2 (ACE2), but they all enhance the RBD’s affinity for mouse ACE2. We further determined the crystal structure of omicron RBD complexed with mouse ACE2. The structure showed that all four mutations are viral adaptations to mouse ACE2: three of them (Q493R, Q498R, and Y505H) are uniquely adapted to mouse ACE2, whereas the other one (N501Y) is adapted to both human ACE2 and mouse ACE2. These data reveal that the omicron RBD was well adapted to mouse ACE2 before omicron started to infect humans, providing insight into the potential evolutionary origin of the omicron variant.

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Section: Discussionmentioning

confidence: 99%

Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant

Zhang

Shi

Geng

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…For cattle, mink and pigs, reports disagree concerning the presence of clinical signs post SARS‐CoV‐2 infection (Schlottau et al, 2020 ; Shi et al, 2020 ; Meekins et al, 2020 ; Ulrich et al, 2020 ; Buckley et al, 2021 ; Falkenberg et al, 2021 ; Pickering et al, 2021 ; Shuai et al, 2021 ; Sikkema et al, 2022 ; Virtanen et al, 2022 ). One out of two references describe fever in cattle; one out of two references describe anorexia, diarrhoea, lethargy and respiratory signs in mink; and fever and ocular discharge was described for pigs in two independent references out of six in total.…”

Section: Assessmentmentioning

confidence: 99%

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

Nielsen¹,

Álvarez²,

Bicout³

et al. 2023

EFS2

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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.

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“…Both dose levels were advanced to efficacy testing after intranasal infection of ferrets with 1 × 10 5 pfu of SARS-CoV-2 isolate USA-WA1/ 2020 (lineage A), which most efficiently replicates and spreads in ferrets 27,29,37,39,40 and other members of the Mustela genus 41,42 . Treatment was initiated 12 h after infection and continued b.i.d., and nasal lavages collected twice daily to determine shed virus load (Fig.…”

Section: Paxlovid Treatment Of Sars-cov-2 Infection In Ferretsmentioning

confidence: 99%

Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models

Cox,

Lieber,

Wolf

et al. 2023

Nat Commun

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Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials suggested greater efficacy of paxlovid, but recent studies indicated comparable potency in older adults. Here, we compare both drugs in two animal models; the Roborovski dwarf hamster model for severe COVID-19-like lung infection and the ferret SARS-CoV-2 transmission model. Dwarf hamsters treated with either drug survive VOC omicron infection with equivalent lung titer reduction. Viral RNA copies in the upper respiratory tract of female ferrets receiving 1.25 mg/kg molnupiravir twice-daily are not significantly reduced, but infectious titers are lowered by >2 log orders and direct-contact transmission is stopped. Female ferrets dosed with 20 or 100 mg/kg nirmatrelvir/ritonavir twice-daily show 1–2 log order reduction of viral RNA copies and infectious titers, which correlates with low nirmatrelvir exposure in nasal turbinates. Virus replication resurges towards nirmatrelvir/ritonavir treatment end and virus transmits efficiently (20 mg/kg group) or partially (100 mg/kg group). Prophylactic treatment with 20 mg/kg nirmatrelvir/ritonavir does not prevent spread from infected ferrets, but prophylactic 5 mg/kg molnupiravir or 100 mg/kg nirmatrelvir/ritonavir block productive transmission. These data confirm reports of similar efficacy in older adults and inform on possible epidemiologic benefit of antiviral treatment.

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Experimental Infection of Mink with SARS-COV-2 Omicron Variant and Subsequent Clinical Disease

Cited by 13 publications

References 9 publications

Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant

Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant

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

Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models

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