Chikungunya virus(CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. L...Chikungunya virus(CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Lycorine, an alkaloid from Amaryllidaceae plants, has antiviral activity against a number of viruses such as coronavirus, flavivirus and enterovirus. In this study, we found that lycorine could inhibit CHIKV in cell culture at a concentration of 10 lmol/L without apparent cytotoxicity. In addition, it exhibited broad-spectrum anti-alphavirus activity, including Sindbis virus(SINV),Semliki Forest virus(SFV), and Venezuelan equine encephalomyelitis virus(VEEV). The time of addition studies indicated that lycorine functions at an early post-entry stage of CHIKV life cycle. The results based on two different CHIKV replicons provided further evidence that lycorine exerts its antiviral activity mainly by inhibiting CHIKV translation.Overall, our study extends the antiviral spectrum of lycorine.展开更多
Dear Editor,Omsk hemorrhagic fever virus(OHFV)belongs to the tickborne virus group within Flavivirus,in Flaviviridae family(Holbrook et al.2005)which consists of several important human pathogens including tick-borne ...Dear Editor,Omsk hemorrhagic fever virus(OHFV)belongs to the tickborne virus group within Flavivirus,in Flaviviridae family(Holbrook et al.2005)which consists of several important human pathogens including tick-borne encephalitis virus(TBEV),Powassan virus(POWV),Louping ill virus(LIV),Langat virus(LGTV)and Kyasnaur Forest disease virus(KFDV)(Yoshii and Holbrook 2009).OHFV is an enveloped virus containing a single-stranded positive-sense RNA genome of approximately 11,000 nucleotides.The genome has a single open reading frame,which encodes three structural proteins[capsid(C),pre-membrane(prM)or membrane(M),and envelop(E)]and seven non-structural proteins(NS1,NS2a,NS2b,NS3,NS4a,NS4b and NS5)between the 5'untranslated region(UTR)and 3'UTR(Chambers et al.1990).展开更多
The lung is the prophylaxis target against SARS-CoV-2 infection,and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen.In this study,we develop a safe and cost...The lung is the prophylaxis target against SARS-CoV-2 infection,and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen.In this study,we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle(VRP)delivery system,to prevent SARS-CoV-2 infections.First,a modified VEEV replicon with two subgenomic(sg)promoters was engineered to translate the light and heavy chains of antibody simultaneously,for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6.Second,the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays.The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice.Overall,our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.展开更多
Dear Editor,Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread rapidly and developed into a global pandemic since its outbreak in December 2019.Currentl...Dear Editor,Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread rapidly and developed into a global pandemic since its outbreak in December 2019.Currently,there is no antiviral treatment available for human use.Numerous compounds,such as remdesivir and chloroquine,have been reported to inhibit SARS-CoV-2 replication effectively in vitro,but for most of them,the in vivo efficacies against SARS-CoV-2 are still under clinical studies,and for chloroquine,a drug with prominent in vitro antiviral activity,it has been found no beneficial effect for COVID-19 patients in the recent largest study.It is thus urgent to speed up large-scale screening to discover drug candidates to treat COVID-19.展开更多
Dear Editor,The prolonged outbreak and spread of coronavirus disease 2019(COVID-19),caused by SARS-CoV-2 poses a great threat to global economic and public health.The protective efficacy of the vaccines based on the s...Dear Editor,The prolonged outbreak and spread of coronavirus disease 2019(COVID-19),caused by SARS-CoV-2 poses a great threat to global economic and public health.The protective efficacy of the vaccines based on the spike protein(S)of SARS-CoV-2 has been compromised by the emergence of variants of concern(VOC).展开更多
基金This work was supported by the National Key Research and Development Program of China(2018YFA0507201)。
文摘Chikungunya virus(CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Lycorine, an alkaloid from Amaryllidaceae plants, has antiviral activity against a number of viruses such as coronavirus, flavivirus and enterovirus. In this study, we found that lycorine could inhibit CHIKV in cell culture at a concentration of 10 lmol/L without apparent cytotoxicity. In addition, it exhibited broad-spectrum anti-alphavirus activity, including Sindbis virus(SINV),Semliki Forest virus(SFV), and Venezuelan equine encephalomyelitis virus(VEEV). The time of addition studies indicated that lycorine functions at an early post-entry stage of CHIKV life cycle. The results based on two different CHIKV replicons provided further evidence that lycorine exerts its antiviral activity mainly by inhibiting CHIKV translation.Overall, our study extends the antiviral spectrum of lycorine.
基金This work was supported by the National Major Science and Technology Project(2018ZX10711001-006)the Wuhan Science and Technology Project(2018201261638501)。
文摘Dear Editor,Omsk hemorrhagic fever virus(OHFV)belongs to the tickborne virus group within Flavivirus,in Flaviviridae family(Holbrook et al.2005)which consists of several important human pathogens including tick-borne encephalitis virus(TBEV),Powassan virus(POWV),Louping ill virus(LIV),Langat virus(LGTV)and Kyasnaur Forest disease virus(KFDV)(Yoshii and Holbrook 2009).OHFV is an enveloped virus containing a single-stranded positive-sense RNA genome of approximately 11,000 nucleotides.The genome has a single open reading frame,which encodes three structural proteins[capsid(C),pre-membrane(prM)or membrane(M),and envelop(E)]and seven non-structural proteins(NS1,NS2a,NS2b,NS3,NS4a,NS4b and NS5)between the 5'untranslated region(UTR)and 3'UTR(Chambers et al.1990).
基金This work was supported by the National Key Research and Development Program of China(2018YFA0507201)The funders had no role in study design,data collection,and interpretation,or the decision to submit the work for publication.
文摘The lung is the prophylaxis target against SARS-CoV-2 infection,and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen.In this study,we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle(VRP)delivery system,to prevent SARS-CoV-2 infections.First,a modified VEEV replicon with two subgenomic(sg)promoters was engineered to translate the light and heavy chains of antibody simultaneously,for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6.Second,the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays.The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice.Overall,our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.
基金supported by the National Key Research and Development Program of China(2018YFA0507201).
文摘Dear Editor,Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread rapidly and developed into a global pandemic since its outbreak in December 2019.Currently,there is no antiviral treatment available for human use.Numerous compounds,such as remdesivir and chloroquine,have been reported to inhibit SARS-CoV-2 replication effectively in vitro,but for most of them,the in vivo efficacies against SARS-CoV-2 are still under clinical studies,and for chloroquine,a drug with prominent in vitro antiviral activity,it has been found no beneficial effect for COVID-19 patients in the recent largest study.It is thus urgent to speed up large-scale screening to discover drug candidates to treat COVID-19.
基金supported by the National Key Research and Development Program of China(2018YFA0507201).
文摘Dear Editor,The prolonged outbreak and spread of coronavirus disease 2019(COVID-19),caused by SARS-CoV-2 poses a great threat to global economic and public health.The protective efficacy of the vaccines based on the spike protein(S)of SARS-CoV-2 has been compromised by the emergence of variants of concern(VOC).
