tetano
Editor, Senior Moderator
Bioorg Chem
. 2021 Jul 22;115:105196.
doi: 10.1016/j.bioorg.2021.105196. Online ahead of print.
Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage
Kun Wang[SUP] 1 [/SUP], Jia-Jing Wu[SUP] 2 [/SUP], Xin-Zhang[SUP] 1 [/SUP], Qing-Xuan Zeng[SUP] 1 [/SUP], Na Zhang[SUP] 1 [/SUP], Wei-Jin Huang[SUP] 2 [/SUP], Sheng Tang[SUP] 1 [/SUP], Yan-Xiang Wang[SUP] 1 [/SUP], Wei-Jia Kong[SUP] 1 [/SUP], You-Chun Wang[SUP] 2 [/SUP], Ying-Hong Li[SUP] 3 [/SUP], Dan-Qing Song[SUP] 4 [/SUP]
Affiliations
Abstract
So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1β, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.
Keywords: Aloperine; COVID-19; Cathepsin B; Cytokine; SARS-CoV-2.
. 2021 Jul 22;115:105196.
doi: 10.1016/j.bioorg.2021.105196. Online ahead of print.
Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage
Kun Wang[SUP] 1 [/SUP], Jia-Jing Wu[SUP] 2 [/SUP], Xin-Zhang[SUP] 1 [/SUP], Qing-Xuan Zeng[SUP] 1 [/SUP], Na Zhang[SUP] 1 [/SUP], Wei-Jin Huang[SUP] 2 [/SUP], Sheng Tang[SUP] 1 [/SUP], Yan-Xiang Wang[SUP] 1 [/SUP], Wei-Jia Kong[SUP] 1 [/SUP], You-Chun Wang[SUP] 2 [/SUP], Ying-Hong Li[SUP] 3 [/SUP], Dan-Qing Song[SUP] 4 [/SUP]
Affiliations
- PMID: 34333425
- DOI: 10.1016/j.bioorg.2021.105196
Abstract
So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1β, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.
Keywords: Aloperine; COVID-19; Cathepsin B; Cytokine; SARS-CoV-2.