Structural Impact of Mutation D614G in SARS-CoV-2 Spike Protein: Enhanced Infectivity and Therapeutic Opportunity.,ACS Medicinal Chemistry Letters

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Structural Impact of Mutation D614G in SARS-CoV-2 Spike Protein: Enhanced Infectivity and Therapeutic Opportunity.
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2020-08-17 , DOI: 10.1021/acsmedchemlett.0c00410
Ariel Fernández _{1,

2,

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Affiliation

With the COVID-19 pandemic, the evolutionary fate of SARS-CoV-2 becomes a matter of utmost concern. Mutation D614G in the spike (S) protein has become dominant, and recent evidence suggests it yields a more stable phenotype with higher transmission efficacy. We carry out a structural analysis that provides mechanistic clues on the enhanced infectivity. The D614G substitution creates a sticky packing defect in subunit S1, promoting its association with subunit S2 as a means to stabilize the structure of S1 within the S1/S2 complex. The results raise the therapeutic possibility of immunologically targeting the epitope involved in stabilizing the G614 phenotype as a means of reducing the infection efficacy of SARS-CoV-2. This therapeutic modality would not a-priori interfere directly with current efforts toward the immunological targeting of the RBD epitope; hence, it could be exploited as a complementary treatment.

中文翻译：

SARS-CoV-2穗蛋白中突变D614G的结构影响：增强的感染力和治疗机会。

随着COVID-19大流行，SARS-CoV-2的进化命运成为最令人关注的问题。穗蛋白（S）蛋白中的突变D614G已占主导地位，最近的证据表明，它可产生更稳定的表型，并具有更高的传播效率。我们进行了结构分析，为增强感染力提供了机械线索。D614G取代会在亚基S1中产生粘性堆积缺陷，从而促进其与亚基S2的缔合，从而使S1 / S2复合物中的S1结构稳定。结果提高了免疫学上靶向稳定G614表型所涉及的表位作为降低SARS-CoV-2感染功效的手段的治疗可能性。这种治疗方式不会先验直接干扰当前对RBD表位进行免疫靶向的努力；因此，它可以作为一种补充疗法。

更新日期：2020-09-10

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