COVID-19感染对小细胞肺癌（SCLC）患者造成严重威胁。然而，该复杂疾病的分子基础尚未阐明。本研究利用公开的COVID-19和SCLC omics数据填补了这一空白，探索了这些疾病交叉点所涉及的关键分子和相关通路。研究结果表明，在SCLC患者中存在402个基因，其表达模式与COVID-19发病机制息息相关。随后的功能富集分析确定了与这些基因显著相关的本体和通路，揭示了有关其潜在生物学、分子和细胞功能的重要见解。蛋白质相互作用网络在四种组合拓扑评估下构建，突出显示SMAD3、CAV1、PIK3R1和FN1是这种复发疾病的主要组分。我们的研究结果表明，这些组分通过触发PI3K-AKT和TGF-β信号通路显著调控这种交叉通路。最后，本研究通过多步骤的计算尝试，从天然资源中鉴定出可潜在抑制这些组分的corylifol A和ginkgetin。因此，本研究的结果提供了关于SCLC和COVID-19共同分子机制的新视角，并为药物研发提供了未来机会。Ramaswamy H. Sarma通讯。

The impact of COVID-19 infection on individuals with small cell lung cancer (SCLC) poses a serious threat. Unfortunately, the molecular basis of this severe comorbidity has yet to be elucidated. The present study addresses this gap utilizing publicly available omics data of COVID-19 and SCLC to explore the key molecules and associated pathways involved in the convergence of these diseases. Findings revealed 402 genes, that exhibited differential expression patterns in SCLC patients and also play a pivotal role in COVID-19 pathogenesis. Subsequent functional enrichment analyses identified relevant ontologies and pathways that are significantly associated with these genes, revealing important insights into their potential biological, molecular and cellular functions. The protein-protein interaction network, constructed under four combinatorial topological assessments, highlighted SMAD3, CAV1, PIK3R1, and FN1 as the primary components to this comorbidity. Our results suggest that these components significantly regulate this cross-talk triggering the PI3K-AKT and TGF-β signaling pathways. Lastly, this study made a multi-step computational attempt and identified corylifol A and ginkgetin from natural sources that can potentially inhibit these components. Therefore, the outcomes of this study offer novel perspectives on the common molecular mechanisms underlying SCLC and COVID-19 and present future opportunities for drug development.Communicated by Ramaswamy H. Sarma.