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.

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Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m7G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. In addition, METTL1 and WDR4 promote ESCC progression via the tRNA m7G methyltransferase activity in vitro and in vivo. Mechanistically, METTL1 or WDR4 knockdown leads to decreased expression of m7G-modified tRNAs and reduces the translation of a subset of oncogenic transcripts enriched in RPTOR/ULK1/autophagy pathway. Furthermore, ESCC models using Mettl1 conditional knockout and knockin mice uncover the essential function of METTL1 in promoting ESCC tumorigenesis in vivo. Our study demonstrates the important oncogenic function of mis-regulated tRNA m7G modification in ESCC, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for ESCC treatment.

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...

Influenza is a major threat to millions of people worldwide. Entry inhibitors are of particular interest for the development of novel therapeutic strategies for influenza. We have previously discovered oleanolic acid (OA) to be a mild influenza hemagglutinin (HA) inhibitor. In this work, inspired by the 3D structure of HA as a homotrimeric receptor, we designed and synthesized 15 OA trimers with different linkers and central region via the copper-catalyzed azide−alkyne cycloaddition reaction. All of the OA trimers were evaluated for their antiviral activities in vitro, and 12c, 12e, 13c, and 13d were observed to exhibit robust potency (IC 50 in the submicromolar range) against influenza A/WSN/33 (H1N1) virus that was stronger than that observed with oseltamivir. In addition, these compounds also displayed strong biological activity against A/Hong Kong/4801/2014 and B/Sichuan/531/2018 (BV). The results of hemagglutination inhibition assays and surface plasmon resonance binding assays suggest that these OA trimers may interrupt the interaction between the HA protein of influenza virus and the host cell sialic acid receptor, thus blocking viral entry. These findings highlight the utility of multivalent OA conjugates to enhance the ligand− target interactions in anti-influenza virus drug design and are also helpful for studying antiviral drugs derived from natural products.

The corona virus disease 2019 (COVID-19) pandemic has become a global health emergency. The spike protein (S-protein) of SARS-CoV-2, consisting of S1 and S2 subunits, is critical to receptor recognition and virus-cell fusion. SARS-CoV-2 binds to host cell receptors via the receptor-binding domain (RBD) of S1, which induces the formation of 6-helical bundle (6-HB) between the two heptad repeats (HRs) in S2, namely HR1 and HR2, and the consequential conformational change of S2, which facilitates the virus-membrane fusion. In December 2020, several effective SARS-CoV-2 vaccines were authorized. However, the emergence of new SARS-CoV-2 strains attenuates the effi cacy of vaccines and neutralization antibodies. (1,2) Reduning Injection (热毒宁注射液, RDN), a p p r o v e d b y t h e C h i n e s e F o o d a n d D r u g Administration in 2005, is a Chinese medicine (CM) prepared from Lonicerae Japonicae Flos, Artemisiae Annuae Herba, and Gardeniae Fructus. CM has

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.

Purpose: We aimed to construct a nonlinear regression model through Extreme Gradient Boost (XGBoost) to predict functional outcome 1 year after surgical decompression for patients with acute spinal cord injury (SCI).Methods: We prospectively enrolled 249 patients with acute SCI from 5 primary orthopedic centers from June 1, 2016, to June 1, 2020. We identified a total of 6 predictors with three aspects: 1) clinical characteristics, including age, American Spinal Injury Association (ASIA) Impairment Scale (AIS) at admission, level of injury and baseline ASIA motor score (AMS); 2) MR imaging, mainly including Brain and Spinal Injury Center (BASIC) score; 3) surgical timing, specifically comparing whether surgical decompression was received within 24 hours or not. We assessed the SCIM score at 1 year after the operation as the functional outcome index. XGBoost was used to build a nonlinear regression prediction model through the method of boosting integrated learning.Results: We successfully constructed a nonlinear regression prediction model through XGBoost and verified the credibility. The average absolute value of the difference between the predicted value and the actual value is 3.72 (t=1.29, P=0.203), ranging from 0 to 8.44. AMS and age ranked first and second in predicting the functional outcome.Conclusion: We verified the feasibility of using XGBoost to construct a nonlinear regression prediction model for the functional outcome of patients with acute SCI, and we found that age and AMS play the most important role in predicting the functional outcome.Trial registration: ClinicalTrials.gov identifier: NCT03103516.