The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses
Acute respiratory infections are a group of diseases caused by viruses, bacteria, and parasites that mainly affect children until the age of 5 and immunocompromised senior adults. In Mexico, these infections are the main cause of morbidity in children, with more than 26 million cases of respiratory...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125135/full |
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| author | Uriel Cruz Meza Norvell Perezbusta Lara Laura Chávez Gómez Marcela Solís Rodríguez Javier R. Ambrosio Hernández Rocio Tirado Mendoza |
| author_facet | Uriel Cruz Meza Norvell Perezbusta Lara Laura Chávez Gómez Marcela Solís Rodríguez Javier R. Ambrosio Hernández Rocio Tirado Mendoza |
| author_sort | Uriel Cruz Meza |
| collection | DOAJ |
| description | Acute respiratory infections are a group of diseases caused by viruses, bacteria, and parasites that mainly affect children until the age of 5 and immunocompromised senior adults. In Mexico, these infections are the main cause of morbidity in children, with more than 26 million cases of respiratory infections reported by the Secretariat of Health, in 2019. The human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV), and the human parainfluenza-2 (hPIV-2) are responsible for many respiratory infections. Currently, palivizumab, a monoclonal antibody against the fusion protein F, is the treatment of choice against hRSV infections. This protein is being studied for the design of antiviral peptides that act by inhibiting the fusion of the virus and the host cell. Therefore, we examined the antiviral activity of the HRA2pl peptide, which competes the heptad repeat A domain of the F protein of hMPV. The recombinant peptide was obtained using a viral transient expression system. The effect of the fusion peptide was evaluated with an in vitro entry assay. Moreover, the effectiveness of HRA2pl was examined in viral isolates from clinical samples obtained from patients with infections caused by hRSV, hMPV, or hPIV-2, by evaluating the viral titer and the syncytium size. The HRA2pl peptide affected the viruses’ capacity of entry, resulting in a 4-log decrease in the viral titer compared to the untreated viral strains. Additionally, a 50% reduction in the size of the syncytium was found. These results demonstrate the antiviral potential of HRA2pl in clinical samples, paving the way toward clinical trials. |
| first_indexed | 2024-04-09T17:11:47Z |
| format | Article |
| id | doaj.art-a5f2fc7d26f34ba78b6769587a0d9959 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-09T17:11:47Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-a5f2fc7d26f34ba78b6769587a0d99592023-04-20T05:58:12ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-04-011310.3389/fcimb.2023.11251351125135The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumovirusesUriel Cruz Meza0Norvell Perezbusta Lara1Laura Chávez Gómez2Marcela Solís Rodríguez3Javier R. Ambrosio Hernández4Rocio Tirado Mendoza5Department of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City, MexicoDepartment of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City, MexicoDepartment of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City, MexicoPharmaceutical Chemistry Department, University of Kansas, Douglas, KS, United StatesDepartment of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City, MexicoDepartment of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City, MexicoAcute respiratory infections are a group of diseases caused by viruses, bacteria, and parasites that mainly affect children until the age of 5 and immunocompromised senior adults. In Mexico, these infections are the main cause of morbidity in children, with more than 26 million cases of respiratory infections reported by the Secretariat of Health, in 2019. The human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV), and the human parainfluenza-2 (hPIV-2) are responsible for many respiratory infections. Currently, palivizumab, a monoclonal antibody against the fusion protein F, is the treatment of choice against hRSV infections. This protein is being studied for the design of antiviral peptides that act by inhibiting the fusion of the virus and the host cell. Therefore, we examined the antiviral activity of the HRA2pl peptide, which competes the heptad repeat A domain of the F protein of hMPV. The recombinant peptide was obtained using a viral transient expression system. The effect of the fusion peptide was evaluated with an in vitro entry assay. Moreover, the effectiveness of HRA2pl was examined in viral isolates from clinical samples obtained from patients with infections caused by hRSV, hMPV, or hPIV-2, by evaluating the viral titer and the syncytium size. The HRA2pl peptide affected the viruses’ capacity of entry, resulting in a 4-log decrease in the viral titer compared to the untreated viral strains. Additionally, a 50% reduction in the size of the syncytium was found. These results demonstrate the antiviral potential of HRA2pl in clinical samples, paving the way toward clinical trials.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125135/fullacute respiratory infectionshuman respiratory virusparamyxoviruspneumovirusfusion peptidesyncytium size |
| spellingShingle | Uriel Cruz Meza Norvell Perezbusta Lara Laura Chávez Gómez Marcela Solís Rodríguez Javier R. Ambrosio Hernández Rocio Tirado Mendoza The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses Frontiers in Cellular and Infection Microbiology acute respiratory infections human respiratory virus paramyxovirus pneumovirus fusion peptide syncytium size |
| title | The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses |
| title_full | The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses |
| title_fullStr | The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses |
| title_full_unstemmed | The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses |
| title_short | The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses |
| title_sort | hra2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses |
| topic | acute respiratory infections human respiratory virus paramyxovirus pneumovirus fusion peptide syncytium size |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125135/full |
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