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COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut–lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus , Bacteroides oleiciplenus , Fusobacterium ulcerans , and Prevotella bivia. The abundances of Bacteroides stercoris , B. vulgatus , B. massiliensis , Bifidobacterium longum , Streptococcus thermophilus , Lachnospiraceae bacterium 5163FAA, Prevotella bivia , Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile , Streptococcus salivarius , Coprococcus catus , Eubacterium hallii , Enterobacter aerogenes , and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman's correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19. [ABSTRACT FROM AUTHOR]

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread globally to over 200 countries with more than 23 million confirmed cases and at least 800,000 fatalities as of 23 August 2020. Declared a pandemic on March 11 by World Health Organization, the disease caused by SARS‐CoV‐2 infection, called coronavirus disease 2019 (COVID‐19), has become a global public health crisis that challenged all national healthcare systems. This review summarized the current knowledge about virologic and pathogenic characteristics of SARS‐CoV‐2 with emphasis on potential immunomodulatory mechanism and drug development. With multiple emerging technologies and cross‐disciplinary approaches proving to be crucial in our global response against COVID‐19, the application of PROteolysis TArgeting Chimeras strategy, CRISPR‐Cas9 gene editing technology, and Single‐Nucleotide‐Specific Programmable Riboregulators technology in developing antiviral drugs and detecting infectious diseases are proposed here. We also discussed the available but still limited epidemiology of COVID‐19 as well as the ongoing efforts on vaccine development. In brief, we conducted an in‐depth analysis of the pathogenesis of SARS‐CoV‐2 and reviewed the therapeutic options for COVID‐19. We also proposed key research directions in the future that may help uncover more underlying molecular mechanisms governing the pathology of COVID‐19. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 μM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 μM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19. [ABSTRACT FROM AUTHOR]