Doi Akihiro, Tomita Yuriko, Okura Hiyori, Matsuyama Shutoku
Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan.
PNAS Nexus. 2022 Sep 20;1(4):pgac197. doi: 10.1093/pnasnexus/pgac197. eCollection 2022 Sep.
Mutations in nonstructural protein 3 (nsp3) and nsp4 of SARS-CoV-2, presumably induced by the asthma drug ciclesonide (which also has anti-SARS-CoV-2 activity), were counted 5,851 cases in the GISAID EpiCoV genome database. Sporadic occurrence of mutants not linked to each other in the phylogenetic tree were identified at least 88 times; of which, 58 had one or more descendants in the same branch. Five of these had spread to more than 100 cases, and one had expanded to 4,748 cases, suggesting the mutations are frequent, selected in individual patients, and transmitted to form clusters of cases. Clinical trials of ciclesonide as a treatment for COVID-19 are the presumed cause of the frequent occurrence of mutations between 2020 June and 2021 November. In addition, because ciclesonide is a common treatment for asthma, it can drive mutations in asthmatics suffering from COVID-19. Ciclesonide-resistant mutations, which have unpredictable effects in humans, are likely to continue to emerge because SARS-CoV-2 remains prevalent globally.
据推测，由哮喘药物环索奈德（该药物也具有抗SARS-CoV-2活性）诱导的新型冠状病毒非结构蛋白3（nsp3）和nsp4突变，在全球共享流感数据倡议组织（GISAID）的EpiCoV基因组数据库中有5851例记录。在系统发育树中，至少88次发现了彼此不相关的突变体散发病例；其中，58例在同一分支中有一个或多个后代。其中5例已传播至100多例，1例已扩展至4748例，这表明这些突变很常见，在个体患者中被选择，并传播形成病例集群。环索奈德作为治疗新冠肺炎的临床试验被认为是2020年6月至2021年11月期间频繁发生突变的原因。此外，由于环索奈德是治疗哮喘的常用药物，它可能会导致感染新冠肺炎的哮喘患者发生突变。由于新型冠状病毒在全球仍然流行，对环索奈德耐药的突变可能会继续出现，而这些突变对人类的影响是不可预测的。
