Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States
Despite the rapid mass vaccination against COVID-19, the emergence of new SARS-CoV-2 variants of concern, such as omicron, is still a great distress, and new therapeutic options are needed. Bovine lactoferrin (bLf), a multifunctional iron-binding glycoprotein available in unsaturated (apo-bLf) and s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1352 |
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| author | Nathalia S. Alves Adriana S. Azevedo Brenda M. Dias Ingrid S. Horbach Bruno P. Setatino Caio B. Denani Waleska D. Schwarcz Sheila Maria B. Lima Sotiris Missailidis Ana Paula D. Ano Bom Andréa M. V. Silva Débora F. Barreto Vieira Marcos Alexandre N. Silva Caroline A. Barros Carlos Alberto M. Carvalho Rafael B. Gonçalves |
| author_facet | Nathalia S. Alves Adriana S. Azevedo Brenda M. Dias Ingrid S. Horbach Bruno P. Setatino Caio B. Denani Waleska D. Schwarcz Sheila Maria B. Lima Sotiris Missailidis Ana Paula D. Ano Bom Andréa M. V. Silva Débora F. Barreto Vieira Marcos Alexandre N. Silva Caroline A. Barros Carlos Alberto M. Carvalho Rafael B. Gonçalves |
| author_sort | Nathalia S. Alves |
| collection | DOAJ |
| description | Despite the rapid mass vaccination against COVID-19, the emergence of new SARS-CoV-2 variants of concern, such as omicron, is still a great distress, and new therapeutic options are needed. Bovine lactoferrin (bLf), a multifunctional iron-binding glycoprotein available in unsaturated (apo-bLf) and saturated (holo-bLf) forms, has been shown to exert broad-spectrum antiviral activity against many viruses. In this study, we evaluated the efficacy of both forms of bLf at 1 mg/mL against infection of Vero cells by SARS-CoV-2. As assessed with antiviral assays, an equivalent significant reduction in virus infection by about 70% was observed when either form of bLf was present throughout the infection procedure with the SARS-CoV-2 ancestral or omicron strain. This inhibitory effect seemed to be concentrated during the early steps of virus infection, since a significant reduction in its efficiency by about 60% was observed when apo- or holo-bLf were incubated with the cells before or during virus addition, with no significant difference between the antiviral effects of the distinct iron-saturation states of the protein. However, an ultrastructural analysis of bLf treatment during the early steps of virus infection revealed that holo-bLf was somewhat more effective than apo-bLf in inhibiting virus entry. Together, these data suggest that bLf mainly acts in the early events of SARS-CoV-2 infection and is effective against the ancestral virus as well as its omicron variant. Considering that there are no effective treatments to COVID-19 with tolerable toxicity yet, bLf shows up as a promising candidate. |
| first_indexed | 2024-03-10T20:58:50Z |
| format | Article |
| id | doaj.art-8e15f7404df94333b778ae4b531330de |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:58:50Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-8e15f7404df94333b778ae4b531330de2023-11-19T17:41:15ZengMDPI AGPharmaceuticals1424-82472023-09-011610135210.3390/ph16101352Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation StatesNathalia S. Alves0Adriana S. Azevedo1Brenda M. Dias2Ingrid S. Horbach3Bruno P. Setatino4Caio B. Denani5Waleska D. Schwarcz6Sheila Maria B. Lima7Sotiris Missailidis8Ana Paula D. Ano Bom9Andréa M. V. Silva10Débora F. Barreto Vieira11Marcos Alexandre N. Silva12Caroline A. Barros13Carlos Alberto M. Carvalho14Rafael B. Gonçalves15Instituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilLaboratório de Morfologia e Morfogênese Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilLaboratório de Morfologia e Morfogênese Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Patologia, Centro de Ciências Biológicas e da Saúde, Universidade do Estado do Pará, Belém 66095-662, PA, BrazilDepartamento de Bioquímica, Instituto Biomédico, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20211-040, RJ, BrazilDespite the rapid mass vaccination against COVID-19, the emergence of new SARS-CoV-2 variants of concern, such as omicron, is still a great distress, and new therapeutic options are needed. Bovine lactoferrin (bLf), a multifunctional iron-binding glycoprotein available in unsaturated (apo-bLf) and saturated (holo-bLf) forms, has been shown to exert broad-spectrum antiviral activity against many viruses. In this study, we evaluated the efficacy of both forms of bLf at 1 mg/mL against infection of Vero cells by SARS-CoV-2. As assessed with antiviral assays, an equivalent significant reduction in virus infection by about 70% was observed when either form of bLf was present throughout the infection procedure with the SARS-CoV-2 ancestral or omicron strain. This inhibitory effect seemed to be concentrated during the early steps of virus infection, since a significant reduction in its efficiency by about 60% was observed when apo- or holo-bLf were incubated with the cells before or during virus addition, with no significant difference between the antiviral effects of the distinct iron-saturation states of the protein. However, an ultrastructural analysis of bLf treatment during the early steps of virus infection revealed that holo-bLf was somewhat more effective than apo-bLf in inhibiting virus entry. Together, these data suggest that bLf mainly acts in the early events of SARS-CoV-2 infection and is effective against the ancestral virus as well as its omicron variant. Considering that there are no effective treatments to COVID-19 with tolerable toxicity yet, bLf shows up as a promising candidate.https://www.mdpi.com/1424-8247/16/10/1352antiviral activitylactoferrinSARS-CoV-2 |
| spellingShingle | Nathalia S. Alves Adriana S. Azevedo Brenda M. Dias Ingrid S. Horbach Bruno P. Setatino Caio B. Denani Waleska D. Schwarcz Sheila Maria B. Lima Sotiris Missailidis Ana Paula D. Ano Bom Andréa M. V. Silva Débora F. Barreto Vieira Marcos Alexandre N. Silva Caroline A. Barros Carlos Alberto M. Carvalho Rafael B. Gonçalves Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States Pharmaceuticals antiviral activity lactoferrin SARS-CoV-2 |
| title | Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States |
| title_full | Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States |
| title_fullStr | Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States |
| title_full_unstemmed | Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States |
| title_short | Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States |
| title_sort | inhibition of sars cov 2 infection in vero cells by bovine lactoferrin under different iron saturation states |
| topic | antiviral activity lactoferrin SARS-CoV-2 |
| url | https://www.mdpi.com/1424-8247/16/10/1352 |
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