Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor

According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.

On the origin of SARS-CoV-2——The blind watchmaker argument

In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.

A highly efficient in vivo plasmid editing tool based on CRISPR-Cas12a and phage λ Red recombineering

Plasmids are useful tools for studying genetic information in living cells,as well as heterologous expression of genes and pathways in cells(Lauritsen et al.,2018).Various methods have been developed for plasmid manipulation both in vivo and in vitro(Aslanidis and de Jong,1990;Li and Elledge,2007;Xia et al.,2018).However,large plasmids,such as P1-based artificial chromosomes(PACs),bacterial artificial chromosomes(BACs),and fosmids,are difficult to manipulate.

Evolutionary dynamics of the severe acute respiratory syndrome coronavirus 2 genomes

The coronavirus disease 2019(COVID-19)pandemic has caused immense losses in human lives and the global economy and posed significant challenges for global public health.As severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of COVID-19,has evolved,thousands of single nucleotide variants(SNVs)have been identified across the viral genome.The roles of individual SNVs in the zoonotic origin,evolution,and transmission of SARS-CoV-2 have become the focus of many studies.This review summarizes recent comparative genomic analyses of SARS-CoV-2 and related coronaviruses(SC2r-CoVs)found in non-human animals,including delineation of SARS-CoV-2 lineages based on characteristic SNVs.We also discuss the current understanding of receptor-binding domain(RBD)evolution and characteristic mutations in variants of concern(VOCs)of SARS-CoV-2,as well as possible co-evolution between RBD and its receptor,angiotensin-converting enzyme 2(ACE2).We propose that the interplay between SARS-CoV-2 and host RNA editing mechanisms might have partially resulted in the bias in nucleotide changes during SARS-CoV-2 evolution.Finally,we outline some current challenges,including difficulty in deciphering the complicated relationship between viral pathogenicity and infectivity of different variants,and monitoring transmission of SARS-CoV-2 between humans and animals as the pandemic progresses.