Antibody-dependent enhancement (ADE) exists in several kinds of virus. It has a negative influence on antibody therapy for viral infection. This effect was first identified in dengue virus and has since also been described for coronavirus. To date, the rapid spread of the newly emerged coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has affected over 3.8 million people across the globe. The novel coronavirus poses a great challenge and has caused a wave of panic. In this review, antibody-dependent enhancements in dengue virus and two kinds of coronavirus are summarized. Possible solutions for the effects are reported. We also speculate that ADE may exist in SARS-CoV-2.
RNA N6-methyladenosine is a key step of posttranscriptional modulation that is involved in governing gene expression. The m6A modification catalyzed by Mettl3 has been widely recognized as a critical epigenetic regulation process for tumorigenic properties in various cancer cell lines, including bladder cancer. However, the in vivo function of Mettl3 in bladder cancer remains largely unknown. In our study, we found that ablation of Mettl3 in bladder urothelial attenuates the oncogenesis and tumor angiogenesis of bladder cancer using transgenic mouse model. In addition, conditional knockout of Mettl3 in K14+ bladder cancer stem cell population leads to inhibition of bladder cancer progression. Coupled with the global transcriptome sequencing and methylated RNA immunoprecipitation sequencing results, we showed that deletion of Mettl3 leads to the suppression of tyrosine kinase endothelial (TEK) and vascular endothelial growth factor A (VEGF-A) through reduced abundance of m6A peaks on a specific region. In addition, the depletion of Mettl3 results in the decrease in both messenger RNA (mRNA) and protein levels of TEK and VEGF-A in vitro. Taken together, Mettl3-mediated m6A modification is required for the activation of TEK–VEGF-A-mediated tumor progression and angiogenesis. Our findings may provide theoretical basis for bladder cancer treatment targeting Mettl3.
The coronavirus disease 2019 is a new type of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. COVID-19 is affecting millions of patients, and the infected number keeps increasing. SARS-CoV-2 is highly infectious, has a long incubation period, and causes a relatively high death rate, resulting in severe health problems all over the world. Currently there is no effective proven drug for the treatment of COVID-19; therefore, development of effective therapeutic drugs to suppress SARS-CoV-2 infection is urgently needed. In this review, we first summarize the structure and genome features of SARS-CoV-2 and introduce its infection and replication process. Then, we review the clinical symptoms, diagnosis, and treatment options of COVID-19 patients. We further discuss the potential molecular targets and drug development strategies for treatment of the emerging COVID-19. Finally, we summarize clinical trials of some potential therapeutic drugs and the results of vaccine development. This review provides some insights for the treatment of COVID-19.The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now affecting millions of patients all over the world as of May 30, 2020. 1,2 According to World Health Organization (WHO) statistics on March 3, the mortality rate among confirmed COVID-19 cases was 3.4%. As of May 22, according to Worldometer, the mortality rate is nearly 5.9%. In Italy, however, the mortality rate is more than 13%. The SARS-CoV-2 coronavirus is a type of single-stranded RNA virus that belongs to the coronaviruses family. [2][3][4] Coronaviruses can be divided into four genera: Alphacoronavirus (aCoV), Betacoronavirus (bCoV), Gammacoronavirus (gCoV), and Deltacoronavirus (dCoV). 5 Currently, seven coronaviruses are known to infect human, including two alphacoronaviruses (HCoV-229E and HKU-NL63) and five betacoronaviruses (HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). During the past two decades, three previously unknown betacoronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) have emerged. 6 These deadly coronaviruses cause lower respiratory tract infections, resulting in acute pneumonia, respiratory distress, cytokine storms, multiple organ dysfunctions, and even patient death. 1,7,8 In this review, we highlight the pandemic of the emerging COVID-19, review the key molecular and clinical characteristics of SARS-CoV-2, and discuss the potential options for developing drugs for the treatment of COVID-19. Genomic Structure and Viral Protein Characteristics of SARS-CoV-2The genome of SARS-CoV-2 contains 29,903 nt (NCBI: NC_045512.2), of which the GC content is 38%. The SARS-CoV-2 genome encodes about 9,860 aa. Similar to other coronaviruses, the SARS-CoV-2 genome consists of two flanked untranslated regions (UTRs), a 5 0 long open reading frame (ORF1a/b) that encodes polyproteins, and several structural protein-encoding ORFs (Figure 1). [9][10][11] The polyprotein encoded by 5 0 ORF1a/b is cleaved...
Limbal stem cells are essential for continuous corneal regeneration and injury repair. METTL3-catalyzed N6-methyladenosine (m6A) mRNA modifications are involved in many biological processes and play a specific role in stem cell regeneration, while the role of m6A modifications in corneal injury repair remains unknown. In this study, we generated a limbal stem cell-specific METTL3 knockout mouse model and studied the role of m6A in repairing corneal injury caused by alkali burn. The results showed that METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DDIT4 as m6A targets. Our study reveals the essential functions of m6A RNA modification in regulating injury repair and provides novel insights for clinical therapy of corneal diseases.
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