Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 16610 Prague, Czech Republic.
Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296/70, 62100 Brno, Czech Republic.
Molecules. 2022 Mar 15;27(6):1894. doi: 10.3390/molecules27061894.
Positive-sense single-stranded RNA (+RNA) viruses have proven to be important pathogens that are able to threaten and deeply damage modern societies, as illustrated by the ongoing COVID-19 pandemic. Therefore, compounds active against most or many +RNA viruses are urgently needed. Here, we present PR673, a helquat-like compound that is able to inhibit the replication of SARS-CoV-2 and tick-borne encephalitis virus in cell culture. Using in vitro polymerase assays, we demonstrate that PR673 inhibits RNA synthesis by viral RNA-dependent RNA polymerases (RdRps). Our results illustrate that the development of broad-spectrum non-nucleoside inhibitors of RdRps is feasible.
正链单链 RNA（+RNA）病毒已被证明是重要的病原体，能够威胁和严重破坏现代社会，正如正在发生的 COVID-19 大流行所表明的那样。因此，迫切需要针对大多数或许多 +RNA 病毒有效的化合物。在这里，我们介绍了 PR673，一种类似 helquat 的化合物，能够在细胞培养中抑制 SARS-CoV-2 和蜱传脑炎病毒的复制。通过体外聚合酶测定，我们证明 PR673 抑制病毒 RNA 依赖性 RNA 聚合酶（RdRps）的 RNA 合成。我们的结果表明，开发 RdRps 的广谱非核苷抑制剂是可行的。
