Small molecules in the treatment of COVID-19
Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-12-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-022-01249-8 |
| _version_ | 1811302175392923648 |
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| author | Sibei Lei Xiaohua Chen Jieping Wu Xingmei Duan Ke Men |
| author_facet | Sibei Lei Xiaohua Chen Jieping Wu Xingmei Duan Ke Men |
| author_sort | Sibei Lei |
| collection | DOAJ |
| description | Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed. |
| first_indexed | 2024-04-13T07:23:19Z |
| format | Article |
| id | doaj.art-3b2fac88dea0432985d43d5e6fb4f925 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-04-13T07:23:19Z |
| publishDate | 2022-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-3b2fac88dea0432985d43d5e6fb4f9252022-12-22T02:56:33ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352022-12-017113910.1038/s41392-022-01249-8Small molecules in the treatment of COVID-19Sibei Lei0Xiaohua Chen1Jieping Wu2Xingmei Duan3Ke Men4State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityDepartment of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityDepartment of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityAbstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.https://doi.org/10.1038/s41392-022-01249-8 |
| spellingShingle | Sibei Lei Xiaohua Chen Jieping Wu Xingmei Duan Ke Men Small molecules in the treatment of COVID-19 Signal Transduction and Targeted Therapy |
| title | Small molecules in the treatment of COVID-19 |
| title_full | Small molecules in the treatment of COVID-19 |
| title_fullStr | Small molecules in the treatment of COVID-19 |
| title_full_unstemmed | Small molecules in the treatment of COVID-19 |
| title_short | Small molecules in the treatment of COVID-19 |
| title_sort | small molecules in the treatment of covid 19 |
| url | https://doi.org/10.1038/s41392-022-01249-8 |
| work_keys_str_mv | AT sibeilei smallmoleculesinthetreatmentofcovid19 AT xiaohuachen smallmoleculesinthetreatmentofcovid19 AT jiepingwu smallmoleculesinthetreatmentofcovid19 AT xingmeiduan smallmoleculesinthetreatmentofcovid19 AT kemen smallmoleculesinthetreatmentofcovid19 |