High thermoelectric performance at room temperature of n-type Mg_(3)Bi_(2)-based materials by Se doping

Bi_(2)Te_(3) based alloys have been the most widely used thermoelectric material at low temperature for many decades.Here we report Se doped n-type Mg_(3)Bi_(2) based materials with a thermoelectric figure-of-merit ZT of 0.82 at 300 K and a peak ZT of 1.24 at 498 K,which is comparable to the n-type Bi_(2)Te_(3) and Te doped Mg_(3)Bi_(1.4)Sb_(0.6).The improved thermoelectric performance is benefited from the high carrier concentration and mobility as well as the thermal conductivity reduction.The reduced resistivity increased the power factor at all measured temperatures,leading to a higher engineering ZT(ZTeng)and engineering power factor(PFeng)for n-type Mg_(3)Bi_(2).The n-type Mg_(3)Bi_(1.4)Sb_(0.6) materials are promising for thermoelectric power generation and cooling applications near room temperature.

Electrical property enhancement and lattice thermal conductivity reduction of n-type Mg_(3)Sb_(1.5)Bi_(0.5)-based Zintl compound by In&Se co-doping

Mg_(3)Sb_(1.5)Bi_(0.5)-based Zintl compounds have attracted extensive attention as potential thermoelectric materials due to their earth-abundant elements.However,pure and intrinsic Mg_(3)Sb_(1.5)Bi_(0.5)manifests a poor thermoelectric performance because of its low electrical conductivity of about 3×10^(2)S/m at room temperature.In this work,In and Se co-doping was carried out to optimize the thermoelectric perfor-mance of n-type Mg_(3)Sb_(1.5)Bi_(0.5)-based material.The experimental results revealed that the carrier con-centration and mobility of Mg_(3)Sb_(1.5)Bi_(0.5)significantly increased after In and Se co-doping,leading to an improvement of power factor.Simultaneously,lattice thermal conductivity was significantly reduced due to the large mass difference between In and Mg.A maximum zT of 1.64 at 723 K was obtained for the Mg_(3.17)In_(0.03)Sb_(1.5)Bi_(0.49)Se_(0.01)sample.And an average zT value of about 1.1 between 300 and 723 K was achieved,which insures its possible application at medium temperature range as a non-toxic and low-cost TE material.

Peptide targeting the interaction of S protein cysteine-rich domain with Ezrin restricts pan-coronavirus infection

Dear Editor,To date,seven human coronaviruses(HCoVs)have been identified,among which the highly pathogenic severe acute respiratory syndrome-associated coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)have caused public health disasters worldwide.

SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis

The coronavirus disease 2019(COVID-19)pandemic has devastated global health.Identifying key host factors essential for SARS-CoV-2 RNA replication is expected to unravel cellular targets for the development of broad-spectrum antiviral drugs which have been quested for the preparedness of future viral outbreaks.Here,we have identified host proteins that associate with nonstructural protein 12(nsp12),the RNA-dependent RNA polymerase(RdRp)of SARS-CoV-2 using a mass spectrometry(MS)-based proteomic approach.Among the candidate factors,CDK2(Cyclin-dependent kinase 2),a member of cyclin-dependent kinases,interacts with nsp12 and causes its phosphorylation at T20,thus facilitating the assembly of the RdRp complex consisting of nsp12,nsp7 and nsp8 and promoting efficient synthesis of viral RNA.The crucial role of CDK2 in viral RdRp function is further supported by our observation that CDK2 inhibitors potently impair viral RNA synthesis and SARS-CoV-2 infection.Taken together,we have discovered CDK2 as a key host factor of SARS-CoV-2 RdRp complex,thus serving a promising target for the development of SARS-CoV-2 RdRp inhibitors.

SARS-CoV-2 nsp12 attenuates type Ⅰ interferon production by inhibiting IRF3 nuclear translocation

SARS-CoV-2 is the pathogenic agent of COVID-19,which has evolved into a global pandemic.Compared with some other respiratory RNA viruses,SARS-CoV-2 is a poor inducer of type Ⅰ interferon(IFN).Here,we report that SARS-CoV-2 nsp12,the viral RNA-dependent RNA polymerase(RdRp),suppresses host antiviral responses.SARS-CoV-2 nsp12 attenuated Sendai virus(SeV)-or poly(I:C)-induced IFN-β promoter activation in a dose-dependent manner.It also inhibited IFN promoter activation triggered by RIG-I,MDA5,MAVS,and IRF3 overexpression.Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3.Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12.Given these findings,our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.

Construction of Non-infectious SARS-CoV-2 Replicons and Their Application in Drug Evaluation

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists all over the world have made great efforts to this end.However,manipulation of the SARS-CoV-2 should be performed in the biosafety level3 laboratory.This makes experiments complicated and time-consuming.Therefore,a safer system for working with this virus is urgently needed.Here,we report the construction of plasmid-based,non-infectious SARS-CoV-2 replicons with turbo-green fluorescent protein and/or firefly luciferase reporters by reverse genetics using transformation-associated recombination cloning in Saccharomyces cerevisiae.Replication of these replicons was achieved simply by direct transfection of cells with the replicon plasmids as evident by the expression of reporter genes.Using SARS-CoV-2 replicons,the inhibitory effects of E64-D and remdesivir on SARS-CoV-2 replication were confirmed,and the halfmaximal effective concentration(EC50)value of remdesivir and E64-D was estimated by different quantification methods respectively,indicating that these SARS-CoV-2 replicons are useful tools for antiviral drug evaluation.

Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) has become one major threat to human population health.The RNA-dependent RNA polymerase(RdRp) presents an ideal target of antivirals,whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus.Herein,we report that corilagin(RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp,binds directly to RdRp,effectively inhibits the polymerase activity in both cell-free and cell-based assays,fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration(EC50) value of 0.13 μmol/L.Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp.In addition,combination of RAI-S-37 with remdesivir exhibits additive activity against antiSARS-CoV-2 RdRp.Together with the current data available on the safety and pharmacokinetics of corilagin as a medicinal herbal agent,these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.

Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection

The global coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a positive-sense RNA virus.How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved.Here,we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway.SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation.cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection.We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion.Furthermore,cytoplasmic chromatin-cGAS-STING pathway,but not MAVS-mediated viral RNA sensing pathway,contributes to interferon and pro-inflammatory gene expression upon cell fusion.Finally,we show that cGAS is required for host antiviral responses against SARS-CoV-2,and a STING-activating compound potently inhibits viral replication.Together,our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection,mediated by cytoplasmic chromatin from the infected cells.Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19.In addition,these findings extend our knowledge in host defense against viral infection by showing that host cells’self-nucleic acids can be employed as a“danger signal”to alarm the immune system.

Screening for inhibitors against SARS-CoV-2 and its variants

Severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)continues to evolve,generating new variants that pose a threat to global health;therefore,it is imperative to obtain safe and broad‐spectrum antivirals against SARS‐CoV‐2 and its variants.To this end,we screened compounds for their ability to inhibit viral entry,which is a critical step in virus infection.Twenty compounds that have been previously reported to inhibit SARS‐CoV‐2 replication were tested by using pseudoviruses containing the spike protein from the original strain(SARS‐CoV‐2‐WH01).The cytotoxicity of these compounds was determined.Furthermore,we identified six compounds with strong antagonistic activity against the WH01 pseudovirus,and low cytotoxicity was identified.These compounds were then evaluated for their efficacy against pseudoviruses expressing the spike protein from B.1.617.2(Delta)and B.1.1.529(Omicron),the two most prevalent circulating strains.These assays demonstrated that two phenothiazine compounds,trifluoperazine 2HCl and thioridazine HCl,inhibit the infection of Delta and Omicron pseudoviruses.Finally,we discovered that these two compounds were highly effective against authentic SARS‐CoV‐2 viruses,including the WH01,Delta,and Omicron strains.Our study identified potential broad‐spectrum SARS‐CoV‐2 inhibitors and provided insights into the development of novel therapeutics.