tetano
Editor, Senior Moderator
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 (3CL[SUP]pro[/SUP]) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection
Lei Tian[SUP] 1 [/SUP], Taotao Qiang[SUP] 2 [/SUP], Xiuding Yang[SUP] 3 [/SUP], Yue Gao[SUP] 4 [/SUP], Xiaopei Zhai[SUP] 5 [/SUP], Kairui Kang[SUP] 3 [/SUP], Cong Du[SUP] 3 [/SUP], Qi Lu[SUP] 3 [/SUP], Hong Gao[SUP] 6 [/SUP], Dezhu Zhang[SUP] 7 [/SUP], Xiaolin Xie[SUP] 8 [/SUP], Chengyuan Liang[SUP] 9 [/SUP]
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 (3CL[SUP]pro[/SUP]), 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 3CL[SUP]pro[/SUP] 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 3CL[SUP]pro[/SUP] 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 (3CL[SUP]pro[/SUP]) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection
Lei Tian[SUP] 1 [/SUP], Taotao Qiang[SUP] 2 [/SUP], Xiuding Yang[SUP] 3 [/SUP], Yue Gao[SUP] 4 [/SUP], Xiaopei Zhai[SUP] 5 [/SUP], Kairui Kang[SUP] 3 [/SUP], Cong Du[SUP] 3 [/SUP], Qi Lu[SUP] 3 [/SUP], Hong Gao[SUP] 6 [/SUP], Dezhu Zhang[SUP] 7 [/SUP], Xiaolin Xie[SUP] 8 [/SUP], Chengyuan Liang[SUP] 9 [/SUP]
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 (3CL[SUP]pro[/SUP]), 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 3CL[SUP]pro[/SUP] 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 3CL[SUP]pro[/SUP] 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.