Monticelli Maria, Hay Mele Bruno, Benetti Elisa, Fallerini Chiara, Baldassarri Margherita, Furini Simone, Frullanti Elisa, Mari Francesca, Andreotti Giuseppina, Cubellis Maria Vittoria, Renieri Alessandra
Department of Biology, Università Federico II, 80126 Napoli, Italy.
Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy.
Genes (Basel). 2021 Apr 19;12(4):596. doi: 10.3390/genes12040596.
The protease encoded by the gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients-young males and elderly women-and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of or inhibiting protein activity.
该基因编码的蛋白酶促进病毒感染，并与SARS-CoV-2的发病机制有关。我们分析了该序列，并将蛋白质变体与意大利1177名新冠肺炎患者队列的临床特征相关联。鉴定出九个相对常见的变体（等位基因频率>0.01）和六个错义变体，根据HumVar训练模式下的PolyPhen-2，这些变体可能影响蛋白酶活性。其中，p.V197M（p.Val197Met）（rs12329760）是一种常见变体，对蛋白酶有有害影响，对患者有保护作用。其作用在两个患者亚组——年轻男性和老年女性——以及合并症患者中显得尤为重要，在疾病轻度受影响且无需住院或吸氧治疗的个体中，该变体频率高于那些受影响更严重、需要吸氧治疗、通气或插管的个体。本研究为识别有发展为重症新冠肺炎风险的患者提供了有用信息，并鼓励使用影响该基因表达或抑制蛋白质活性的药物。
