破解新冠病毒谜题支撑疫情科学防控

新型冠状病毒肺炎疫情在全球范围内已持续两年多,深刻地影响着人类社会的各个方面。各国科技工作者对新型冠状病毒(简称“新冠病毒”)开展了广泛而深入的研究,在新冠病毒的感染致病机理、诊断技术、疫苗药物等方面取得了积极的进展。经过两年多的全球流行,病毒持续传播与变异,人类面临着疫苗保护力下降、药物有效性不足等诸多挑战。本综述主要介绍我们团队在新冠病毒的发现鉴定、传播途径、诊断新技术、疫苗药物、亚基因组生成调控机制等方面的研究进展,以期为疫情防控提供科技支撑和参考依据。

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,we identified two potent inhibitors of human DHODH,S312 and S416,with favorable drug-likeness and pharmacokinetic profiles,which all showed broad-spectrum antiviral effects against various RNA viruses,including influenza A virus,Zika virus,Ebola virus,and particularly against SARS-CoV-2.Notably,S416 is reported to be the most potent inhibitor so far with an EC5o of 17 nmol/L and an SI value of 10,505.88 in infec-ted cells.Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells.This work demonstrates that both S312/S416 and old drugs(Leflunomide/Teriflunomide)with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide,no matter such viruses are mutated or not.

Antibody neutralization to SARS-CoV-2 and variants after 1 year in Wuhan,China

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity,but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants.Here,we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan,the earliest known epicenter.SARS-CoV-2 immunoglobulin G(IgG)was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant.However,varying degrees of immune escape was observed on the other tested variants in a patient-specific manner,with individuals showing remarkably broad neutralization potency.The immune escape can be largely attributed to several critical spike mutations.These results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

Correction to:Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

CORRECTION TO:PROTEIN CELL 2020,11(10):723–739 HTTPS://DOI.ORG/10.1007/S13238-020-00768-W In the original publication the author’s name‘Dimitri Lavillete’is published incorrectly.The correct author name should be spelt as‘Dimitri Lavillette’is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit http://creativecommons.org/licenses/by/4.0/.

Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Figure 1.Discovery of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and S416.The detailed descriptions of the discovery workflow are in Method.Binding analysis of S312(B)and S416(C).Thermodynamic analysis of the binding of S312 and S416 to DHODH was carried out at 25 C on a MicroCal iTC200 instrument.Kinetic analysis of the binding of S312 and S416 to DHODH was performed with a Biacore T200 instrument.

A Study of Two Cases Co-Infected with SARS-CoV-2 and Human Immunodeficiency Virus

Dear Editor,Since December 2019,A new type of coronavirus pneumonia(coronavirus disease 2019,COVID-19)has become endemic in Wuhan,China.So far,COVID-19 has developed into a global epidemic.The body’s immune system plays an important role in the fight against COVID-19.