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Eur J Med Chem
. 2023 Nov 25:264:115979.
doi: 10.1016/j.ejmech.2023.115979. Online ahead of print. Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection
Lei Tian 1 , Taotao Qiang 2 , Xiuding Yang 3 , Yue Gao 4 , Xiaopei Zhai 5 , Kairui Kang 3 , Cong Du 3 , Qi Lu 3 , Hong Gao 6 , Dezhu Zhang 7 , Xiaolin Xie 8 , Chengyuan Liang 9
Affiliations
Although no longer a public health emergency of international concern, COVID-19 remains a persistent and critical health concern. The development of effective antiviral drugs could serve as the ultimate piece of the puzzle to curbing this global crisis. 3-chymotrypsin-like protease (3CLpro), with its substrate specificity mirroring that of the main picornavirus 3C protease and conserved across various coronaviruses, emerges as an ideal candidate for broad-spectrum antiviral drug development. Moreover, it holds the potential as a reliable contingency option to combat emerging SARS-CoV-2 variants. In this light, the approved drugs, promising candidates, and de-novo small molecule therapeutics targeting 3CLpro since the COVID-19 outbreak in 2020 are discussed. Emphasizing the significance of diverse structural characteristics in inhibitors, be they peptidomimetic or nonpeptidic, with a shared mission to minimize the risk of cross-resistance. Moreover, the authors propose an innovative optimization strategy for 3CLpro reversible covalent PROTACs, optimizing pharmacodynamics and pharmacokinetics to better prepare for potential future viral outbreaks.
Keywords: 3-Chymotrypsin-like protease (3CL(pro)); COVID-19; Coronavirus; Picornavirus; Proteolysis-targeting chimeras (PROTACs); SARS-CoV-2.
. 2023 Nov 25:264:115979.
doi: 10.1016/j.ejmech.2023.115979. Online ahead of print. Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection
Lei Tian 1 , Taotao Qiang 2 , Xiuding Yang 3 , Yue Gao 4 , Xiaopei Zhai 5 , Kairui Kang 3 , Cong Du 3 , Qi Lu 3 , Hong Gao 6 , Dezhu Zhang 7 , Xiaolin Xie 8 , Chengyuan Liang 9
Affiliations
- PMID: 38048696
- DOI: 10.1016/j.ejmech.2023.115979
Although no longer a public health emergency of international concern, COVID-19 remains a persistent and critical health concern. The development of effective antiviral drugs could serve as the ultimate piece of the puzzle to curbing this global crisis. 3-chymotrypsin-like protease (3CLpro), with its substrate specificity mirroring that of the main picornavirus 3C protease and conserved across various coronaviruses, emerges as an ideal candidate for broad-spectrum antiviral drug development. Moreover, it holds the potential as a reliable contingency option to combat emerging SARS-CoV-2 variants. In this light, the approved drugs, promising candidates, and de-novo small molecule therapeutics targeting 3CLpro since the COVID-19 outbreak in 2020 are discussed. Emphasizing the significance of diverse structural characteristics in inhibitors, be they peptidomimetic or nonpeptidic, with a shared mission to minimize the risk of cross-resistance. Moreover, the authors propose an innovative optimization strategy for 3CLpro reversible covalent PROTACs, optimizing pharmacodynamics and pharmacokinetics to better prepare for potential future viral outbreaks.
Keywords: 3-Chymotrypsin-like protease (3CL(pro)); COVID-19; Coronavirus; Picornavirus; Proteolysis-targeting chimeras (PROTACs); SARS-CoV-2.