Evolution of host protease interactions among SARS-CoV-2 variants of concern and related coronaviruses.
Evolution of host protease interactions among SARS-CoV-2 variants of concern and related coronaviruses.
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所关注的 SARS-CoV-2 变体和相关冠状病毒之间宿主蛋白酶相互作用的演变。
DOI：
10.1101/2022.06.16.496428
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Cantley,LewisC
中科院分区：
文献类型：
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作者：
Kastenhuber,EdwardR;Johnson,JaredL;Yaron,TomerM;Mercadante,Marisa;Cantley,LewisC
先前，我们发现凝血因子直接切割SARS-CoV-2刺突并促进病毒进入（Kastenhuber et al., 2022）。在这里，我们发现在SARS-CoV-2关注变异（VOCs）中观察到的S1/S2切割位点的取代与宿主蛋白酶（包括Xa因子和furin）表现出不同的相互作用。那莫司他仍然有效阻断凝血因子介导的变异穗序列的裂解。此外，宿主蛋白酶的使用可能是冠状病毒进化过程中的一种选择压力，我们观察到远亲冠状病毒趋同以实现共同的宿主蛋白酶相互作用，包括凝血因子。对新出现的SARS-CoV-2变体和未来人畜共患外溢的基因组监测的解释得到了反复出现的新特征的功能表征的支持。
Previously, we showed that coagulation factors directly cleave SARS-CoV-2 spike and promote viral entry (Kastenhuber et al., 2022). Here, we show that substitutions in the S1/S2 cleavage site observed in SARS-CoV-2 variants of concern (VOCs) exhibit divergent interactions with host proteases, including factor Xa and furin. Nafamostat remains effective to block coagulation factor-mediated cleavage of variant spike sequences. Furthermore, host protease usage has likely been a selection pressure throughout coronavirus evolution, and we observe convergence of distantly related coronaviruses to attain common host protease interactions, including coagulation factors. Interpretation of genomic surveillance of emerging SARS-CoV-2 variants and future zoonotic spillover is supported by functional characterization of recurrent emerging features.