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SARS-CoV-2 proteins

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    Comparative in vitro transcriptomic analyses of COVID-19 MESHD candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes.

    Authors: Michael Jay Corley; Christopher Sugai; Michael Schotsaert; Robert E. Schwartz; Lishomwa C Ndhlovu

    doi:10.1101/2020.04.13.039263 Date: 2020-04-14 Source: bioRxiv

    Hydroxychloroquine (HCQ) has emerged as a potential and controversial antiviral candidate therapy for COVID-19 MESHD. While many clinical trials are underway to test the efficacy of HCQ as a treatment for COVID-19 MESHD, underlying mechanisms of HCQ in the setting of COVID-19 MESHD remain unclear. Hence, we examined differential gene expression signatures of HCQ exposure, in vitro SARS-CoV-2 infection MESHD, and host signatures of COVID-19 MESHD in blood, bronchoalveolar lavage, and postmortem lung to evaluate whether HCQ transcriptome signatures associate with restoration of SARS-CoV-2-related host transcriptional responses. Here, we show that 24 hours of in vitro treatment of peripheral blood mononuclear cells(PBMC) with HCQ significantly impacted transcription of 16 genes involved in immune regulation and lipid metabolism. Using transcriptome data from in vitro SARS-CoV-2 infected MESHD NHBE and A549 cells and PBMC derived from confirmed COVID-19 MESHD infected MESHD patients, we determined that only 0.24% of the COVID-19 MESHD PBMC differentially expressed gene set and 0.39% of the in vitro SARS-CoV-2 cells differentially expressed gene set overlapped with HCQ-related differentially expressed genes. Moreover, we observed that HCQ treatment significantly impacted transcription of 159 genes in human primary monocyte-derived macrophages involved in cholesterol biosynthetic process and chemokine activity. Notably, when we compared the macrophage HCQ-related gene lists with genes transcriptionally altered during SARS-CoV-2 infection MESHD and in bronchoalveolar lavage of COVID-19 MESHD+ patients, the CXCL6 HGNC gene was impacted in all three transcriptional signatures revealing evidence in favor of chemokine modulation. HCQ-related transcriptional changes minimally overlapped with host genes altered in postmortem lung biopsies from COVID-19 MESHD participants. These results may provide insight into the immunomodulation mechanisms of HCQ treatment in the setting of COVID-19 MESHD and suggest HCQ is not a panacea to SARS-CoV-2 infection MESHD.

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MeSH Disease
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SARS-CoV-2 Proteins


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