The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2
Arenaviruses and coronaviruses include several human pathogenic viruses, such as Lassa virus, Lymphocytic choriomeningitis virus (LCMV), SARS-CoV, MERS-CoV, and SARS-CoV-2. Although these viruses belong to different virus families, they possess a common motif, the DED/EDh motif, known as an exonucle...
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MDPI AG
2021-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/7/1220 |
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| author | Mya Myat Ngwe Tun Kouichi Morita Takeshi Ishikawa Shuzo Urata |
| author_facet | Mya Myat Ngwe Tun Kouichi Morita Takeshi Ishikawa Shuzo Urata |
| author_sort | Mya Myat Ngwe Tun |
| collection | DOAJ |
| description | Arenaviruses and coronaviruses include several human pathogenic viruses, such as Lassa virus, Lymphocytic choriomeningitis virus (LCMV), SARS-CoV, MERS-CoV, and SARS-CoV-2. Although these viruses belong to different virus families, they possess a common motif, the DED/EDh motif, known as an exonuclease (ExoN) motif. In this study, proof-of-concept studies, in which the DED/EDh motif in these viral proteins, NP for arenaviruses, and nsp14 for coronaviruses, could be a drug target, were performed. Docking simulation studies between two structurally different chemical compounds, ATA and PV6R, and the DED/EDh motifs in these viral proteins indicated that these compounds target DED/EDh motifs. The concentration which exhibited modest cell toxicity was used with these compounds to treat LCMV and SARS-CoV-2 infections in two different cell lines, A549 and Vero 76 cells. Both ATA and PV6R inhibited the post-entry step of LCMV and SARS-CoV-2 infection. These studies strongly suggest that DED/EDh motifs in these viral proteins could be a drug target to combat two distinct viral families, arenaviruses and coronaviruses. |
| first_indexed | 2024-03-10T10:05:55Z |
| format | Article |
| id | doaj.art-cc08899f505645938b791d8be85f0d04 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T10:05:55Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-cc08899f505645938b791d8be85f0d042023-11-22T01:32:11ZengMDPI AGViruses1999-49152021-06-01137122010.3390/v13071220The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2Mya Myat Ngwe Tun0Kouichi Morita1Takeshi Ishikawa2Shuzo Urata3Department of Virology, Institute of Tropical Medicine and Leading Program, Graduate School of Biomedical Science, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanDepartment of Virology, Institute of Tropical Medicine and Leading Program, Graduate School of Biomedical Science, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanDepartment of Chemistry, Biotechnology and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, JapanNational Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanArenaviruses and coronaviruses include several human pathogenic viruses, such as Lassa virus, Lymphocytic choriomeningitis virus (LCMV), SARS-CoV, MERS-CoV, and SARS-CoV-2. Although these viruses belong to different virus families, they possess a common motif, the DED/EDh motif, known as an exonuclease (ExoN) motif. In this study, proof-of-concept studies, in which the DED/EDh motif in these viral proteins, NP for arenaviruses, and nsp14 for coronaviruses, could be a drug target, were performed. Docking simulation studies between two structurally different chemical compounds, ATA and PV6R, and the DED/EDh motifs in these viral proteins indicated that these compounds target DED/EDh motifs. The concentration which exhibited modest cell toxicity was used with these compounds to treat LCMV and SARS-CoV-2 infections in two different cell lines, A549 and Vero 76 cells. Both ATA and PV6R inhibited the post-entry step of LCMV and SARS-CoV-2 infection. These studies strongly suggest that DED/EDh motifs in these viral proteins could be a drug target to combat two distinct viral families, arenaviruses and coronaviruses.https://www.mdpi.com/1999-4915/13/7/1220Lymphocytic choriomeningitis virus (LCMV)SARS-CoV-2antiviralsexonuclease (ExoN) motifDED/EDh motif |
| spellingShingle | Mya Myat Ngwe Tun Kouichi Morita Takeshi Ishikawa Shuzo Urata The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2 Viruses Lymphocytic choriomeningitis virus (LCMV) SARS-CoV-2 antivirals exonuclease (ExoN) motif DED/EDh motif |
| title | The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2 |
| title_full | The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2 |
| title_fullStr | The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2 |
| title_full_unstemmed | The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2 |
| title_short | The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2 |
| title_sort | antiviral effect of the chemical compounds targeting ded edh motifs of the viral proteins on lymphocytic choriomeningitis virus and sars cov 2 |
| topic | Lymphocytic choriomeningitis virus (LCMV) SARS-CoV-2 antivirals exonuclease (ExoN) motif DED/EDh motif |
| url | https://www.mdpi.com/1999-4915/13/7/1220 |
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