In a new study in Cell Discovery, Liang Li and Chen-Yu Zhang group at Nanjing University and two other groups report that SIDT1 polymorphism remarkably decreases HD-MIR2911 absorption in human. Exosome isolated from volunteers that carry SIDT1 polymorphism has lower level of HD-MIR2911 and fails to inhibit of SARS-CoV-2 replication.
Previously, Chen-Yu Zhang's group have identified SID1 transmembrane family member 1 (SIDT1) as a critical membrane protein mediating dietary miRNAs absorption, which is abolished in SIDT1 deficient mice. In the present study, they demonstrate a significant frequency of human population (16%) that carry a SIDT1 polymorphism with amino acid replacement (Val78Met). Functional analysis reveals that such polymorphism (SIDT1poly) undermines its low pH-dependent uptake of exogenous miRNAs in vitro compared to wildtype SIDT1 protein. Additionally, people with SIDT1poly have lower serum levels of exogenous miRNAs (~10%) compared to SIDT1wt group. Dynamic absorption of MIR2911 after oral administration of honeysuckle decoction also significantly declines in SIDT1poly population. These findings suggest the critical role of SIDT1 in dietary miRNAs uptake in human. Furthermore, people with SIDT1poly have lower level of MIR2911 both in serum and isolated exosomes. The exosome from those polymorphic subjects show no effects on S-protein expression or virus replication. Notably, one out of six SARS-CoV-2 patients we observed who takes significantly longer time (17 days versus average 3.8 days) to become SARS-CoV-2 PCR-negative after MIR2911 antiviral therapy carries the exact polymorphism (SIDT1-Val78Met). Although it needs larger number of human subjects to strengthen the conclusions, it clearly shows that MIR2911 is indispensable to the antiviral effect of honeysuckle decoction.
- 1. This study provides evidence that SIDT1 medias dietary miRNAs uptake in human, which further confirm its critical role in exogenous miRNAs absorption.
2. Combined with their previous finding, it is clearly showed that MIR2911 is both necessary and sufficient to the antiviral effects of honeysuckle decoction against SARS-CoV-2.
"We have demonstrated that absorbed MIR2911 in honeysuckle decoction necessarily and sufficiently inhibits SARS-CoV-2 replication in vitro and in human subjects". Liang Li said. "Therefore, we wish that people could discard prejudice to traditional medicine and perform clinic trail to help controlling COVID-19 pandemic. Basically, you reject MIR2911 in honeysuckle decoction, you reject life". Liang Li added.
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The researchers of this project include Zhen Zhou, Yu Zhou, Xia-Ming Jiang, Yanbo Wang, Xi Chen, Gengfu Xiao, Chen-Yu Zhang, Yongxiang Yi, Lei-Ke Zhang and Liang Li of Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life Sciences, Nanjing University, State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Department of critical Care Medicine and Nanjing infectious Disease Center, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine.
This work was supported by grants from the Chinese Science and Technology Major Project of China (2015ZX09102023-003), National Key Research and Development Plan (2018YFA0507100), National Basic Research Program of China (973 Program) (2014CB542300 and 2012CB517603), National Natural Science Foundation of China (81250044, 81602697 and 31741075), the Natural Science Foundation of Jiangsu Province (BE2016737) and the Fundamental Research Funds for the Central Universities (020814380130, 020814380133, 020814380137 and 020814380146).
Zhou et al.: "Decreased HD-MIR2911 absorption in human subjects with the SIDT1 polymorphism fails to inhibit SARS-CoV-2 replication"
Publishing on Cell Discovery 11 September 2020
Author contact: Prof. Chen-Yu Zhang (Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), NJU Institute of Artificial Intelligence Biomedicine, School of Life Sciences, Nanjing University, China) Tel: +86-25-89680245 Email: cyzhang@nju.edu.cn
Journal
Cell Discovery