Small molecules in the treatment of COVID-19

Lei et al., Signal Transduction and Targeted Therapy, doi:10.1038/s41392-022-01249-8, NCT04468139, Dec 2022

https://c19early.org/lei.html

Review of small molecule therapeutics for COVID-19, focusing on antiviral drugs and immunomodulatory agents. The review covers multiple therapeutic strategies including direct viral protein inhibition (targeting RdRp and M^pro), interference with host enzymes like ACE2 and proteases, and blocking immunoregulatory pathways such as JAK/STAT, BTK, NF-κB, and NLRP3 to address cytokine storm. Authors examine nucleoside/nucleotide analogs, protease inhibitors, flavonoids and terpenoids, and host protease inhibitors targeting TMPRSS2 and cathepsin L.

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Lei et al., 5 Dec 2022, USA, peer-reviewed, 5 authors, trial NCT04468139 (history). Contact: duanxingmei2003@163.com, mendingbob@hotmail.com.

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Abstract: Signal Transduction and Targeted Therapy REVIEW ARTICLE www.nature.com/sigtrans OPEN Small molecules in the treatment of COVID-19 Sibei Lei1, Xiaohua Chen2, Jieping Wu1, Xingmei Duan2 ✉ and Ke Men1 ✉ 1234567890();,: 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. Signal Transduction and Targeted Therapy (2022)7:387

DOI record: { "DOI": "10.1038/s41392-022-01249-8", "ISSN": [ "2059-3635" ], "URL": "http://dx.doi.org/10.1038/s41392-022-01249-8", "abstract": "AbstractThe 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. 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