The SARS-CoV2 (COVID-19) pandemic and uncertainties in developing a vaccine have created an urgent need for new therapeutic approaches. A key question is whether it is possible to make rational predictions of new therapies based on the presently available scientific and medical information. In this regard, I have noticed an omission in the present analysis in the literature related to the exploitation of glycogen synthase kinase 3 (GSK-3) as a therapeutic approach. This is based on two key observations, that GSK-3 inhibitors can simultaneously block SARs viral replication, while boosting CD8+ adaptive T-cell and innate natural killer (NK) responses. Firstly, it is already clear that GSK-3 phosphorylation of SARs CoV1 N protein on key serine residues is needed for viral replication such that small molecule inhibitors (SMIs) of GSK-3 can inhibit viral replication. In comparing protein sequences, I show here that the key sites in the N protein of SARs CoV1 N for replication are conserved in SARs CoV2. This strongly suggests that GSK-3 SMIs will also inhibit SARs Cov2 replication. Secondly, we and others have previously documented that GSK-3 SMIs markedly enhance CD8+ cytolytic T-cell (CTL) and NK cell anti-viral effector functions leading to a reduction in both acute and chronic viral infections in mice. My hypothesis is that the repurposing of low-cost inhibitors of GSK-3 such as lithium will limit SARS-CoV2 infections by both reducing viral replication and potentiating the immune response against the virus. To date, there has been no mention of this dual connection between GSK-3 and SARs CoV2 in the literature. To my knowledge, no other drugs exist with the potential to simultaneously target both viral replication and immune response against SARs CoV2.

SARS-CoV2（COVID-19）大流行和疫苗开发的不确定性迫切需要新的治疗方法。一个关键问题是，是否有可能根据目前可用的科学和医学信息对新疗法进行合理的预测。在这方面，我已经注意到在本分析中与利用糖原合酶激酶3（GSK-3）作为治疗方法有关的文献中有遗漏。这基于两个关键的观察结果，即GSK-3抑制剂可同时阻断SARs病毒复制，同时增强CD8 +适应性T细胞和先天性自然杀伤（NK）反应。首先，已经很清楚，病毒复制需要在关键丝氨酸残基上的SARs CoV1 N蛋白进行GSK-3磷酸化，这样GSK-3的小分子抑制剂（SMI）才能抑制病毒复制。在比较蛋白质序列时，我在这里显示SARs CoV1 N的N蛋白中用于复制的关键位点在SARs CoV2中是保守的。这强烈表明，GSK-3 SMI也将抑制SAR Cov2复制。其次，我们和其他人先前已证明GSK-3 SMI显着增强CD8 +溶细胞性T细胞（CTL）和NK细胞抗病毒效应子的功能，从而导致小鼠急性和慢性病毒感染的减少。我的假设是，低成本的GSK-3抑制剂（如锂）的重新使用将通过减少病毒复制和增强针对病毒的免疫反应来限制SARS-CoV2感染。迄今为止，文献中没有提及GSK-3与SAR CoV2之间的这种双重联系。据我所知，没有其他药物可以同时靶向病毒复制和针对SARs CoV2的免疫反应。