Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication.
Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication.
复制标题
DOI：
10.3390/v15071539
复制
发表时间：
2023-07-13
期刊：
影响因子：
--
通讯作者：
Biersack B
中科院分区：
文献类型：
--
作者：
Asthana A;Corona A;Shin WJ;Kwak MJ;Gaughan C;Tramontano E;Jung JU;Schobert R;Jha BK;Silverman RH;Biersack B
Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound (1c) and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound 1c strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3′-to-5′ exoribonuclease (ExoN). While 1c inhibited SARS-CoV-2 ExoN activity, it did not interfere with the mRNA methyltransferase activity of nsp14. In silico molecular docking placed compound 1c in the catalytic pocket of the ExoN domain of nsp14. Finally, 1c inhibited SARS-CoV-2 replication but had no toxicity to human lung adenocarcinoma cells. Given its simple chemical synthesis from easily available starting materials, these results suggest that 1c might be a lead compound for the design of new antiviral compounds that target coronavirus nsp14 ExoN and other viral ribonucleases.
登录
查看更多内容
DOI：
10.3390/pathogens11030368
发表时间：
2022-03-17
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Al-Awwal N;Dweik F;Mahdi S;El-Dweik M;Anderson SH
通讯作者：
Anderson SH
DOI：
10.1056/nejmoa2116846
发表时间：
2022-01-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gottlieb RL;Vaca CE;Paredes R;Mera J;Webb BJ;Perez G;Oguchi G;Ryan P;Nielsen BU;Brown M;Hidalgo A;Sachdeva Y;Mittal S;Osiyemi O;Skarbinski J;Juneja K;Hyland RH;Osinusi A;Chen S;Camus G;Abdelghany M;Davies S;Behenna-Renton N;Duff F;Marty FM;Katz MJ;Ginde AA;Brown SM;Schiffer JT;Hill JA;GS-US-540-9012 (PINETREE) Investigators
通讯作者：
GS-US-540-9012 (PINETREE) Investigators
影响因子：
7.3
作者：
Ailenberg, M.;Di Ciano-Oliveira, C.;Rotstein, O. D.
通讯作者：
Rotstein, O. D.
影响因子：
4.9
作者：
Corona, Angela;Schneider, Anna;Tramontano, Enzo
通讯作者：
Tramontano, Enzo
DOI：
10.1016/s1473-3099(22)00119-0
发表时间：
2022-08
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Dal-Ré R;Becker SL;Bottieau E;Holm S
通讯作者：
Holm S