Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has become a pandemic, infecting more than 4,000,000 people worldwide. This review describes the main clinical features of COVID-19 and potential role of microbiota in COVID-19. SARS-CoV and SARS-CoV-2 have 79.5% nucleotide sequence identity and use angiotensin-converting enzyme 2 (ACE2) receptors to enter host cells. The distribution of ACE2 may determine how SARS-CoV-2 infects the respiratory and digestive tract. SARS and COVID-19 share similar clinical features, although the estimated fatality rate of COVID-19 is much lower. The communication between the microbiota and SARS-CoV-2 and the role of this association in diagnosis and treatment are unclear. Changes in the lung microbiota were identified in COVID-19 patients, and the enrichment of the lung microbiota with bacteria found in the intestinal tract is correlated with the onset of acute respiratory distress syndrome and long-term outcomes. ACE2 regulates the gut microbiota by indirectly controlling the secretion of antimicrobial peptides. Moreover, the gut microbiota enhances antiviral immunity by increasing the number and function of immune cells, decreasing immunopathology, and stimulating interferon production. In turn, respiratory viruses are known to influence microbial composition in the lung and intestine. Therefore, the analysis of changes in the microbiota during SARS-CoV-2 infection may help predict patient outcomes and allow the development of microbiota-based therapies.

SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted a targeted CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. Here we show that the protein BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenous ACE2 expression and SARS-CoV-2 infection of human cells, including those of human nasal epithelia. Moreover, pharmacological BRD2 inhibition with the drug ABBV-744 inhibited SARS-CoV-2 replication in Syrian hamsters. We also found that BRD2 controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates the antiviral response. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a therapeutic target for COVID-19.

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