Cargando…
A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir
[Image: see text] The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This pept...
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical Society
2022
|
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331150/ https://www.ncbi.nlm.nih.gov/pubmed/35971455 http://dx.doi.org/10.1021/acsmedchemlett.2c00260 |
| _version_ | 1784758331832795136 |
|---|---|
| author | Vankadara, Subramanyam Dawson, Monique Danielle Fong, Jia Yi Oh, Qin Yao Ang, Qi An Liu, Boping Chang, Hong Yun Koh, Judice Koh, Xiaoying Tan, Qian Wen Joy, Joma Chia, Cheng San Brian |
| author_facet | Vankadara, Subramanyam Dawson, Monique Danielle Fong, Jia Yi Oh, Qin Yao Ang, Qi An Liu, Boping Chang, Hong Yun Koh, Judice Koh, Xiaoying Tan, Qian Wen Joy, Joma Chia, Cheng San Brian |
| author_sort | Vankadara, Subramanyam |
| collection | PubMed |
| description | [Image: see text] The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections. |
| format | Online Article Text |
| id | pubmed-9331150 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | American Chemical Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-93311502022-07-28 A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir Vankadara, Subramanyam Dawson, Monique Danielle Fong, Jia Yi Oh, Qin Yao Ang, Qi An Liu, Boping Chang, Hong Yun Koh, Judice Koh, Xiaoying Tan, Qian Wen Joy, Joma Chia, Cheng San Brian ACS Med Chem Lett [Image: see text] The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections. American Chemical Society 2022-07-19 /pmc/articles/PMC9331150/ /pubmed/35971455 http://dx.doi.org/10.1021/acsmedchemlett.2c00260 Text en © 2022 American Chemical Society https://pubs.acs.org/page/vi/chemistry_coronavirus_researchThis article is made available via the ACS COVID-19 subset (https://pubs.acs.org/page/vi/chemistry_coronavirus_research) for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
| spellingShingle | Vankadara, Subramanyam Dawson, Monique Danielle Fong, Jia Yi Oh, Qin Yao Ang, Qi An Liu, Boping Chang, Hong Yun Koh, Judice Koh, Xiaoying Tan, Qian Wen Joy, Joma Chia, Cheng San Brian A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir |
| title | A Warhead
Substitution Study on the Coronavirus Main
Protease Inhibitor Nirmatrelvir |
| title_full | A Warhead
Substitution Study on the Coronavirus Main
Protease Inhibitor Nirmatrelvir |
| title_fullStr | A Warhead
Substitution Study on the Coronavirus Main
Protease Inhibitor Nirmatrelvir |
| title_full_unstemmed | A Warhead
Substitution Study on the Coronavirus Main
Protease Inhibitor Nirmatrelvir |
| title_short | A Warhead
Substitution Study on the Coronavirus Main
Protease Inhibitor Nirmatrelvir |
| title_sort | warhead
substitution study on the coronavirus main
protease inhibitor nirmatrelvir |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331150/ https://www.ncbi.nlm.nih.gov/pubmed/35971455 http://dx.doi.org/10.1021/acsmedchemlett.2c00260 |
| work_keys_str_mv | AT vankadarasubramanyam awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT dawsonmoniquedanielle awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT fongjiayi awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT ohqinyao awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT angqian awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT liuboping awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT changhongyun awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT kohjudice awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT kohxiaoying awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT tanqianwen awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT joyjoma awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT chiachengsanbrian awarheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT vankadarasubramanyam warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT dawsonmoniquedanielle warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT fongjiayi warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT ohqinyao warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT angqian warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT liuboping warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT changhongyun warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT kohjudice warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT kohxiaoying warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT tanqianwen warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT joyjoma warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir AT chiachengsanbrian warheadsubstitutionstudyonthecoronavirusmainproteaseinhibitornirmatrelvir |