Organic and Medicinal Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense, 28040 Madrid, Spain.
Molecules. 2022 Jan 20;27(3):658. doi: 10.3390/molecules27030658.
In spite of advances in vaccination, control of the COVID-19 pandemic will require the use of pharmacological treatments against SARS-CoV2. Their development needs to consider the existence of two phases in the disease, namely the viral infection and the inflammatory stages. The main targets for antiviral therapeutic intervention are: (a) viral proteins, including the spike (S) protein characteristic of the viral cover and the viral proteases in charge of processing the polyprotein arising from viral genome translation; (b) host proteins, such as those involved in the processes related to viral entry into the host cell and the release of the viral genome inside the cell, the elongation factor eEF1A and importins. The use of antivirals targeted at host proteins is less developed but it has the potential advantage of not being affected by mutations in the genome of the virus and therefore being active against all its variants. Regarding drugs that address the hyperinflammatory phase of the disease triggered by the so-called cytokine storm, the following strategies are particularly relevant: (a) drugs targeting JAK kinases; (b) sphingosine kinase 2 inhibitors; (c) antibodies against interleukin 6 or its receptor; (d) use of the traditional anti-inflammatory corticosteroids.
尽管疫苗接种取得了进展,但控制 COVID-19 大流行仍将需要使用针对 SARS-CoV2 的药物治疗。其开发需要考虑疾病存在两个阶段,即病毒感染和炎症阶段。抗病毒治疗干预的主要目标是:(a) 病毒蛋白,包括病毒包膜特征性的刺突 (S) 蛋白和负责处理源自病毒基因组翻译的多蛋白的病毒蛋白酶;(b) 宿主蛋白,如与病毒进入宿主细胞和细胞内释放病毒基因组相关的过程、延伸因子 eEF1A 和导入蛋白。针对宿主蛋白的抗病毒药物的使用尚未得到充分发展,但它具有不受病毒基因组突变影响的潜在优势,因此对其所有变体均有效。关于针对所谓的细胞因子风暴引发的疾病过度炎症阶段的药物,以下策略特别相关:(a) 靶向 JAK 激酶的药物;(b) 鞘氨醇激酶 2 抑制剂;(c) 针对白细胞介素 6 或其受体的抗体;(d) 使用传统的抗炎皮质类固醇。
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