Dataset Information

SARS-CoV2 spike protein gene variants with N501T and G142D mutation-dominated infections in mink in the United States.

ABSTRACT: Large numbers of mink have been infected with SARS-CoV2 containing the spike protein Y453F mutation in Europe, causing zoonosis concerns. To evaluate the genetic characteristics of the U.S. and Canadian mink-derived SARS-CoV2 sequences, we analyzed all animal-derived (977) and all Canadian (19,529) and U.S. (173,277) SARS-CoV2 sequences deposited in GISAID from December 2019 to March 12, 2021, and identified 2 dominant novel variants, the N501T-G142D variant and N501T-G142D-F486L variant, in the U.S. mink-derived SARS-CoV2 sequences. These variants were not found in mink from Canada or other countries. The Y453F mutation was not identified in the mink-derived sequences in the United States and Canada. The N501T mutation occurred 2 mo earlier in humans than in mink in the United States, and the novel N501T-G142D and N501T-G142D-F486L variants were found in humans prior to mink. Our results suggest that the novel SARS-CoV2 variants may have evolved during human infection and were then transmitted to mink populations in the United States.

SUBMITTER: Cai HY

PROVIDER: S-EPMC8366104 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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SARS-CoV2 spike protein gene variants with N501T and G142D mutation-dominated infections in mink in the United States.

Cai Hugh Y HY Cai Allison A

Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 20210610 5

Large numbers of mink have been infected with SARS-CoV2 containing the spike protein Y453F mutation in Europe, causing zoonosis concerns. To evaluate the genetic characteristics of the U.S. and Canadian mink-derived SARS-CoV2 sequences, we analyzed all animal-derived (977) and all Canadian (19,529) and U.S. (173,277) SARS-CoV2 sequences deposited in GISAID from December 2019 to March 12, 2021, and identified 2 dominant novel variants, the N501T-G142D variant and N501T-G142D-F486L variant, in the ...[more]

PMID: 34109885

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Project description: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.

Project description:Background: Attempts to quantify effect sizes of non-pharmaceutical interventions (NPI) to control COVID-19 in the US have not accounted for heterogeneity in social or environmental factors that may influence NPI effectiveness. This study quantifies national and sub-national effect sizes of NPIs during the early months of the pandemic in the US. Methods: Daily county-level COVID-19 cases and deaths during the first wave (January 2020 through phased removal of interventions) were obtained. County-level cases, doubling times, and death rates were compared to four increasingly restrictive NPI levels. Socio-demographic, climate and mobility factors were analyzed to explain and evaluate NPI heterogeneity, with mobility used to approximate NPI compliance. Analyses were conducted separately for the US and for each Census regions (Pacific, Mountain, east/West North Central, East/West South Central, South Atlantic, Middle Atlantic and New England). A stepped-wedge cluster-randomized trial analysis was used, leveraging the phased implementation of policies. Results: Aggressive (level 4) NPIs were associated with slower COVID-19 propagation, particularly in high compliance counties. Longer duration of level 4 NPIs was associated with lower case rates (log beta -0.028, 95% CI -0.04 to -0.02) and longer doubling times (log beta 0.02, 95% CI 0.01-0.03). Effects varied by Census region, for example, level 4 effects on doubling time in Pacific states were opposite to those in Middle Atlantic and New England states. NPI heterogeneity can be explained by differential timing of policy initiation and by variable socio-demographic county characteristics that predict compliance, particularly poverty and racial/ethnic population. Climate exhibits relatively consistent relationships across Census regions, for example, higher minimum temperature and specific humidity were associated with lower doubling times and higher death rates for this period of analysis in South Central, South Atlantic, Middle Atlantic, and New England states. Conclusion and Relevance: Heterogeneity exists in both the effectiveness of NPIs across US Census regions and policy compliance. This county-level variability indicates that control strategies are best designed at community-levels where policies can be tuned based on knowledge of local disparities and compliance with public health ordinances.

Dataset Information

SARS-CoV2 spike protein gene variants with N501T and G142D mutation-dominated infections in mink in the United States.

Publications

SARS-CoV2 spike protein gene variants with N501T and G142D mutation-dominated infections in mink in the United States.

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