Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC

Research progress on host restriction factors of respiratory viruses / 中华实用儿科临床杂志

Respiratory viruses can cause a variety of serious respiratory infections and diseases of tissues and organs outside the respiratory tract, raising a potentially severe threat to the society.Virus replication and survival rely on the internal mechanism of host cells, and the latter also produce a variety of restriction factors that target viral invasion, genome transcription and replication, and assembly and release to block viral infection.Herein, this study reviewed the research progress of the antiviral effects of the host restriction factors of common respiratory viruses and their underlying mechanisms.

Augmentation of anti-MDA5 antibody implies severe disease in COVID-19 patients

OBJECTIVETo identify the anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) in coronavirus disease 2019 (COVID-19) and its relationship with the severity and clinical outcomes of COVID-19. DESIGNRetrospective cohort study. SETTINGThree hospitals in China. PARTICIPANTS274 adult inpatients diagnosed with COVID-19 according to the Protocol for Prevention and Control of COVID-19 (Edition 7) of China and confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA testing, were included from three hospitals from Wuhan, Harbin and Beijing, China from 1 December 2019 to 19 April 2020. The Biobank of Myositis Registry Department of Rheumatology, Peking Union Medical College Hospital, provided the plasma of five patients with anti-MDA5 Ab-related dermatomyositis as positive control group. Demographic, clinical and laboratory data were collected from medical records. The anti-MDA5 Ab was determined by an ELISA assay and was verified by immunoblotting analysis. MAIN OUTCOME MEASURESIn hospital death of all cause. RESULTSThe positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% (132/274) and the anti-MDA5 Ab positive patients tended to represent with severe disease (88.6% vs 66.9%, P<0.0001). The titer of anti-MDA5 Ab was significantly elevated in the non-survivals (5.95{+/-}5.16 vs 8.22{+/-}6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab ([≥]10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. CONCLUSIONAnti-MDA5 Ab was prevalent in the COVID-19 patients and high titer of this antibody is correlated with severe disease and unfavorable outcomes. Early screening and serially monitoring of anti-MDA5 Ab titer have the potential to predict the disease progression of COVID-19.

Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2

COVID-19 pandemic has infected millions of people with mortality exceeding 300,000. There is an urgent need to find therapeutic agents that can help clear the virus to prevent the severe disease and death. Identifying effective and safer drugs can provide with more options to treat the COVID-19 infections either alone or in combination. Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating wide therapeutic window compared to hydroxychloroquine which had safety index of 22 in similar experiments. Mechanistically, five of the effective compounds were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA approved compounds can provide much needed therapeutic options that we urgently need in the midst of the pandemic.Competing Interest StatementThe authors have declared no competing interest.View Full Text

Single-cell transcriptional atlas of the Chinese horseshoe bat (Rhinolophus sinicus) provides insight into the cellular mechanisms which enable bats to be viral reservoirs

Bats are a major "viral reservoir" in nature and there is a great interest in not only the cell biology of their innate and adaptive immune systems, but also in the expression patterns of receptors used for cellular entry by viruses with potential cross-species transmission. To address this and other questions, we created a single-cell transcriptomic atlas of the Chinese horseshoe bat (Rhinolophus sinicus) which comprises 82,924 cells from 19 organs and tissues. This atlas provides a molecular characterization of numerous cell types from a variety of anatomical sites, and we used it to identify clusters of transcription features that define cell types across all of the surveyed organs. Analysis of viral entry receptor genes for known zoonotic viruses showed cell distribution patterns similar to that of humans, with higher expression levels in bat intestine epithelial cells. In terms of the immune system, CD8+ T cells are in high proportion with tissue-resident memory T cells, and long-lived effector memory nature killer (NK) T-like cells (KLRG1, GZMA and ITGA4 genes) are broadly distributed across the organs. Isolated lung primary bat pulmonary fibroblast (BPF) cells were used to evaluate innate immunity, and they showed a weak response to interferon {beta} and tumor necrosis factor- compared to their human counterparts, consistent with our transcriptional analysis. This compendium of transcriptome data provides a molecular foundation for understanding the cell identities, functions and cellular receptor characteristics for viral reservoirs and zoonotic transmission.