Abstract

Despite the continued global spread of the current COVID-19 pandemic, the nonavailability of a vaccine or targeted drug against this disease is still prevailing. The most established mechanism of viral entry into the body is considered to be via angiotensin-converting enzyme 2 (ACE2) acting as a receptor for viral spike protein thereby facilitating its entry in the cell. However, ACE2 is also involved in providing the protection from severe pathological changes. This article provides a computational and bioinformatics-based analysis of ACE2 with an objective of providing further insight into the earnest efforts to determine its true position in COVID-19 pathology. The results of this study show that ACE2 has strikingly low expression in healthy human lung tissue and was absent from the list of differentially expressed genes. However, when transcription factors were analyzed, we found a significant upregulation of FOS and downregulation of FOXO4 and FOXP2. Moreover, the miRNA prediction analysis revealed that miR-1246, whose upregulation has been experimentally established to be a cause of acute respiratory distress syndrome (ARDS), was found to be targeting the coding DNA sequence (CDS) of ACE2. This study presents a wide range of potentially important transcription factors as well as miRNA targets associated with ACE2 which can be potentially used for drug designing amid this challenging pandemic situation.

Communicated by Ramaswamy H. Sarma

摘要

尽管当前 COVID-19 大流行在全球范围内持续蔓延，但针对这种疾病的疫苗或靶向药物仍然无法获得。病毒进入体内最成熟的机制被认为是通过血管紧张素转换酶 2 (ACE2) 作为病毒刺突蛋白的受体，从而促进其进入细胞。然而，ACE2 也参与提供对严重病理变化的保护。本文提供了对 ACE2 的基于计算和生物信息学的分析，目的是进一步深入了解确定其在 COVID-19 病理学中的真正位置的认真努力。这项研究的结果表明，ACE2 在健康人肺组织中的表达非常低，并且不在差异表达基因列表中。然而，当分析转录因子时，我们发现 FOS 显着上调，FOXO4 和 FOXP2 下调。此外，miRNA 预测分析显示，miR-1246 的上调已通过实验确定为急性呼吸窘迫综合征 (ARDS) 的原因，被发现靶向 ACE2 的编码 DNA 序列 (CDS)。这项研究提出了广泛的潜在重要转录因子以及与 ACE2 相关的 miRNA 靶标，这些靶标可潜在地用于在这种具有挑战性的大流行情况下进行药物设计。其上调已通过实验确定是急性呼吸窘迫综合征 (ARDS) 的原因，被发现靶向 ACE2 的编码 DNA 序列 (CDS)。这项研究提出了广泛的潜在重要转录因子以及与 ACE2 相关的 miRNA 靶标，这些靶标可潜在地用于在这种具有挑战性的大流行情况下进行药物设计。其上调已通过实验确定是急性呼吸窘迫综合征 (ARDS) 的原因，被发现靶向 ACE2 的编码 DNA 序列 (CDS)。这项研究提出了广泛的潜在重要转录因子以及与 ACE2 相关的 miRNA 靶标，这些靶标可潜在地用于在这种具有挑战性的大流行情况下进行药物设计。

由 Ramaswamy H. Sarma 传达