AntiCancer, Inc, San Diego, CA, U.S.A.
In Vivo. 2020 Jun;34(3 Suppl):1593-1596. doi: 10.21873/invivo.11948.
The Covid-19 pandemic is a world-wide crisis without an effective therapy. While most approaches to therapy are using repurposed drugs that were developed for other diseases, it is thought that targeting the biology of the SARS-CoV-2 virus, which causes Covid-19, can result in an effective therapeutic treatment. The coronavirus RNA cap structure is methylated by two viral methyltransferases that transfer methyl groups from S-adenosylmethionine (SAM). The proper methylation of the virus depends on the level of methionine in the host to form SAM. Herein, we propose to restrict methionine availability by treating the patient with oral recombinant methioninase, aiming to treat Covid-19. By restricting methionine we not only interdict viral replication, which depends on the viral RNA cap methyaltion, but also inhibit the proliferation of the infected cells, which have an increased requirement for methionine. Most importantly, the virally-induced T-cell- and macrophage-mediated cytokine storm, which seems to be a significant cause for Covid-19 deaths, can also be inhibited by restricting methionine, since T-cell and macrophrage activation greatly increases the methionine requirement for these cells. The evidence reviewed here suggests that oral recombinant methioninase could be a promising treatment for coronavirus patients.
Covid-19 大流行是一场全球性的危机，目前尚无有效的治疗方法。虽然大多数治疗方法都使用了为其他疾病开发的重新利用药物，但人们认为针对导致 Covid-19 的 SARS-CoV-2 病毒的生物学特性可以产生有效的治疗效果。冠状病毒 RNA 帽结构由两种病毒甲基转移酶甲基化，这两种酶将甲基从 S-腺苷甲硫氨酸（SAM）转移。病毒的适当甲基化取决于宿主中甲硫氨酸的水平以形成 SAM。在此，我们建议通过用口服重组甲硫氨酸酶治疗患者来限制甲硫氨酸的可用性，旨在治疗 Covid-19。通过限制甲硫氨酸，我们不仅可以抑制依赖于病毒 RNA 帽甲基化的病毒复制，还可以抑制受感染细胞的增殖，因为受感染细胞对甲硫氨酸的需求增加。最重要的是，病毒诱导的 T 细胞和巨噬细胞介导的细胞因子风暴似乎是导致 Covid-19 死亡的一个重要原因，通过限制甲硫氨酸也可以抑制这种风暴，因为 T 细胞和巨噬细胞的激活大大增加了这些细胞对甲硫氨酸的需求。这里回顾的证据表明，口服重组甲硫氨酸酶可能是治疗冠状病毒患者的一种有前途的治疗方法。
