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Highlights • There are totally five kinds of traditional mechanisms of antibody-dependent enhancement. Mostly, the effect is reported to related with FcγR. • Antibody-dependent enhancement has been discovered in both SARS-CoV and MERS-CoV but the mechanism wasn’t thoroughly clear. Different researches may provide different opinions. • Many scientist have mentioned the potential existence of antibody-dependent enhancement in the 2019 novel coronavirus. • Latest study of both convalescent plasma transmission and application of inactivated vaccine haven’t report case of antibody-dependent enhancement., 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 then was also described for coronavirus. The rapid spread of the newly emerged 2019 novel coronavirus (COVID-19) has sickened over 3.8 million people across the globe up to now. The novel coronavirus causes great challenge and arouses a wave of panic. In this review, antibody-dependent enhancements in dengue virus and two kinds of coronavirus are summarized. Solutions for the effects are mentioned, too. We also speculate that antibody-dependent enhancement may exist in COVID-19.

The coronavirus disease 2019 (COVID-19) 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., Graphical Abstract, With the global pandemic of COVID-19, the development of effective therapeutic drugs and options has become more urgent. In this review, Boxuan Huang et al. mainly focus on the characteristics of COVID-19, the key molecular targets of SARS-CoV-2, relative drug clinical trial results, and progress in vaccine development.

Background: RNA N6-methyladenosine is a key step of post-transcriptional modulation which involves 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. Methods: Establishment of transgenic mouse model for exploring the role and mechanisms of Mettl3 in bladder cancer. Coupled global transcriptome sequencing and methylated RNA immunoprecipitation sequencing is performed to identify targets modulated by Mettl3.Results: We found that ablation of Mettl3 in bladder urothelial attenuates the oncogenesis and tumor angiogenesis of bladder cancer. In addition, conditional knockout of Mettl3 in K14+ bladder cancer stem cell population leads to inhibition of bladder cancer progression. And deletion of Mettl3 leads to the suppression of TEK and VEGF-A through reduced abundance of m6A peaks on specific region. Conclusions: 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.

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.

Highlight • We find that there are highly homology in HR region of SARS-CoV-2 and SARS-CoV. • We firstly used molecular dynamics method in designing antivirus peptide. • Our antivirus peptide can prevent virus membrane fuse with host cell. • Furthermore, we first calculate the binding energy of HR1 and HR2 in SARS-CoV-2 spike protein., An outbreak caused by 2019 novel coronavirus (2019-nCoV) was first identified in Wuhan City, Hubei Province, China. The new virus was later named SARS-CoV-2. The virus has affected tens of thousands of patients in the world. The infection of SARS-CoV-2 causes severe pneumonia and even death. It is urgently needed to find a therapeutic method to treat patients with SARS-CoV-2 infection. Studies showed that the surface spike (S) protein is essential for the coronavirus binding and entry of host cells. The heptad repeats 1 and 2 (HR1 and HR2) in the S protein play a decisive role in the fusion of the viral membrane with the host cell membrane. We predicted the HR1 and HR2 regions in S protein by sequence alignment. We simulated a computational model of HR1/2 regions and the fusion core. The binding energy of HR1 and HR2 of the fusion core was -33.4kCal/mol. We then designed antivirus peptides by molecular dynamics simulation of the fusion core. The binding energy of HR2-based antiviral peptide to HR1 was -43.0kCal/mol, which was stronger than the natural stage of the fusion core, suggesting that the predicted antiviral peptide can competitively bind with HR1 to prevent forming of the fusion core. The antiviral peptides can prevent SARS-CoV-2 membrane fusion and can potentially be used for the prevention and treatment of infections.