Characterization of the receptor-binding domain(RBD)of 2019 novel coronavirus:implication for development of RBD protein as a viral attachment inhibitor and vaccine

The outbreak of Coronavirus Disease 2019(COVID-19)has posed a serious threat to global public health,calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),also known as 2019 novel coronavirus(2019-nCoV).The CoV spike(S)protein plays the most important roles in viral attachment,fusion and entry,and serves as a target for development of antibodies,entry inhibitors and vaccines.Here,we identified the receptor-binding domain(RBD)in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2(ACE2)receptors.SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and,hence,attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells,thus inhibiting their infection to host cells.SARS-CoV RBD-specific antibodies could crossreact with SARS-CoV-2 RBD protein,and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2,suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.

The Hardy Rubber Tree Genome Provides Insights into the Evolution of Polyisoprene Biosynthesis

Eucommia ulmoides, also called hardy rubber tree, is an economically important tree; however, the lack of its genome sequence restricts the fundamental biological research and applied studies of this plant species. Here, we present a high-quality assembly of its ~l.2-Gb genome （scaffold N50 = 1.88 Mb） with at least 26 723 predicted genes for E. ulmoides, the first sequenced genome of the order Garryales, which was obtained using an integrated strategy combining Illumina sequencing, PacBio sequencing, and BioNano mapping. As a sister taxon to lamiids and campanulids, E. ulmoides underwent an ancient genome triplication shared by core eudicots but no further whole-genome duplication in the last ~125 million years. E. ulmoides exhibits high expression levels and/or gene number expansion for multiple genes involved in stress responses and the biosynthesis of secondary metabolites, which may account for its considerable environmental adaptability. In contrast to the rubber tree （Hevea brasiliensis）, which produces cis-polyisoprene, E. ulmoides has evolved to synthe- size long-chain trans-polyisoprene via farnesyl diphosphate synthases （FPSs）. Moreover, FPS and rub- ber elongation factor/small rubber particle protein gene families were expanded independently from the H. brasiliensis lineage. These results provide new insights into the biology of E. ulmoides and the origin of polyisoprene biosynthesis.

Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus

Middle East respiratory syndrome （MERS）, an emerging infectious disease caused by MERS coronavirus （MERS-CoV）, has garnered worldwide attention as a consequence of its continuous spread and pandemic potential, making the development of effective vaccines a high priority. We previously demonstrated that residues 377-588 of MERS-CoV spike （S） protein receptor-binding domain （RBD） is a very promising MERS subunit vaccine candidate, capable of inducing potent neutralization antibody responses. In this study, we sought to identify an adjuvant that optimally enhanced the immunogenicity of S377-588 protein fused with Fc of human IgG （S377-588-Fc）. Specifically, we compared several commercially available adjuvants, including Freund＇s adjuvant, aluminum, Monophosphoryl lipid A, Montanide ISA51 and MF59 with regard to their capacity to enhance the immunogenicity of this subunit vaccine. In the absence of adjuvant, S377-588-Fc alone induced readily detectable neutralizing antibody and T-cell responses in immunized mice. However, incorporating an adjuvant improved its immunogenicity. Particularly, among the aforementioned adjuvants evaluated, MF59 is the most potent as judged by its superior ability to induce the highest titers of IgG, IgG1 and IgG2a subtypes, and neutralizing antibodies. The addition of MF59 significantly augmented the immunogenicity of S377-588-Fcto induce strong IgG and neutralizing antibody responses as well as protection against MERS-CoV infection in mice, suggesting that MF59 is an optimal adjuvant for MERS-CoV RBD-based subunit vaccines.

Roles of the hemagglutinin of influenza A virus in viral entry and development of antiviral therapeutics and vaccines

Seasonal influenza epidemics and influenza pandemics caused by influenza A virus(IAV)has resulted in millions of deaths in the world.The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics.Hemagglutinin(HA)of IAV plays a critical role in viral binding,fusion and entry,and contains the major neutralizing epitopes.Therefore,HA is an attractive target for developing anti-IAV drugs and vaccines.Here we have reviewed the recent progress in study of conformational changes of HA during viral fusion process and development of HA-based antiviral therapeutics and vaccines.

Cross-neutralization of SARS coronavirus-specific antibodies against bat SARS-like coronaviruses

Dear Editor,The 2002–2003 global pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV)infected around 8,000 people with 10%mortality(http://www.who.int/csr/sars/en/).The virus has a positivestranded RNA genome that encodes a large polyprotein(1a and 1ab),four structural proteins,including spike(S),

Neutralizing antibodies for the prevention and treatment of COVID-19

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain(RBD)in the S1 subunit of the viral spike(S)protein.This event is followed by virus–cell membrane fusion mediated by the S2 subunit,which allows virus entry into the host cell.Therefore,the SARS-CoV-2 S protein is a key therapeutic target,and prevention and treatment of coronavirus disease 2019(COVID-19)have focused on the development of neutralizing monoclonal antibodies(nAbs)that target this protein.In this review,we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date,with a focus on the N-terminal domain and RBD of the S protein.We also describe the roles that binding affinity,neutralizing activity,and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARSCoV-2 variants.This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.

Neutralizing antibodies and their cocktails against SARS-CoV-2 Omicron and other circulating variants

Severe acute respiratory coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has led to a pandemic with severe economic losses.The viral surface spike(S)protein comprises two subunits:S1 and S2.S1 contains an N-terminal domain(NTD)and a C-terminal domain(CTD)(i.e.,the receptor binding domain(RBD))[1,2].The RBD itself comprises core and receptor binding motif(RBM)regions(Fig.1a).During virus infection in humans,the RBD of S1 binds to the cellular receptor angiotensin-converting enzyme 2(ACE2)(Fig.1b),and S2 mediates viral entry and membrane fusion[1,3].Thus,the S protein is a critical vaccine and therapeutic target.The prefusion S protein exists as a trimer consisting of three RBDs;of these,the RBD in the“up”confirmation binds to ACE2(Fig.1c).SARS-CoV-2 has undergone frequent mutations since its emergence in 2019,and a number of mutated S protein residues have been identified,including in the RBD.Alpha(B.1.1.7),Beta(B.1.351),and Gamma(P.1)are previously circulating variants of concern(VOCs);in contrast,Delta(B.1.617.2),Omicron(B.1.1.529)BA.1,and other Omicron subvariants(BA.2,BA.3,BA.4,and BA.5),as well as BA.1/BA.2 circulating recombinant forms such as XE,are currently circulating VOC strains[4].Compared with the original SARS-CoV-2,the Omicron variant carries more mutations than any other variant identified thus far,among which approximately 39 and 15 substitutions are within the S protein and RBD,respectively,of the BA.1 subvariant.

Vaccine booster efficiently inhibits entry of SARS-CoV-2 omicron variant

The newly emerged omicron strain of SARS-CoV-2 is spreading fast globally,replacing the previously dominant delta strain in many parts of the world[1].Compared to the early prototypic strains,the delta strain evades the human immune system more easily,causing many breakthrough infections in vaccinated people[2].It is imperative to understand in a timely fashion whether the omicron strain escapes immune surveillances.The information will be critical for public health measures.

Advances in the research and development of therapeutic antibodies against the Zika virus

The Zika virus(ZIKV)is an arbovirus in the same family,Flaviviridae,as the dengue virus(DENV),the West Nile virus,the yellow fever virus,and the Japanese encephalitis virus.ZIKV has been a recent research focus because of its close association with severe human diseases and syndromes,particularly congenital Zika syndrome,which includes fetal microcephaly and other brain abnormalities.1 The ZIKV envelope(E)protein is a major structural protein involved in receptor binding,viral entry,and fusion.It is arranged as a dimer,with each monomer consisting of three domains(DI,DII,and DIII),a stem region,and a transmembrane region.2 The ZIKV E protein induces the production of potent neutralizing antibodies against ZIKV and is thus a key target for the development of therapeutic ZIKV antibodies.

SARS-CoV-2 spike protein: a key target for eliciting persistent neutralizing antibodies

A recent paper published in Science describes the detection of IgG antibody responses in individuals infected by severe acute respiratory syndrome coronavirus(SARS-CoV-2).The authors also examined the duration of antibody production and the correlation between IgG antibody titers and neutralizing antibody titers.1 This study provides information about the kinetics of antibody production,and the functionality and longevity of these antibodies,in patients with Coronavirus Disease 2019(COVID-19).The SARS-CoV-2 genome encodes spike(S),nucleocapsid,membrane,and envelope structural proteins.The S protein plays a key role in viral infection and pathogenesis.