Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is ef...Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.展开更多
Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this ...Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person.We need to revisit this virus to prevent the epidemic from getting worse.In this review,we comprehensively summarize studies on monkeypox,including its epidemiology,biological characteristics,pathogenesis,and clinical characteristics,as well as therapeutics and vaccines,highlighting its unusual outbreak attributed to the transformation of transmission.We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.展开更多
Background:Rare earth elements(REE)are a group of trace elements that behave geochemically coherently.REE fractionation patterns normalized to reference materials provide a powerful tool for documenting pedogenesis.In...Background:Rare earth elements(REE)are a group of trace elements that behave geochemically coherently.REE fractionation patterns normalized to reference materials provide a powerful tool for documenting pedogenesis.Insoil processes are particularly difficult to illustrate with respect to contemporary and past climate conditions.In this study,we characterize the rare earth element(REE)contents in bulk soils and respective geochemical fractions(e.g.,exchangeable,carbonate‑bound,reducible,and oxidizable fractions)and to decipher the relationships between REE geochemistry components and climatic factors across a large‑scale northern China transect(NCT).Results:Across the NCT,bulk REE concentrations ranged from 55.2 to 241.1μg g^(−1)with a main portion in the residual fraction(49–79%),followed by oxidizable fraction(2–40%),reducible fraction(3–22%),carbonate‑bound fraction(0.1–16%),and negligible exchangeable fraction.The REE contents of geochemical components(carbonate‑bound,reducible,and oxidizable)in topsoils correlated to climate factors(mean annual precipitation,mean annual temperature,potential evaporation,and aridity index(AI)).The normalized abundances to the upper continental crust(UCC)composition show that the middle REE was generally enriched than the light REE and heavy REE in topsoils along the transect.The overall UCC‑normalized bulk REE patterns in topsoils and subsoils were similar,characterized by weak negative Ce anomalies and positive Eu anomalies.Conclusions:Our data in topsoils and depth profiles collectively suggest that cycling of REE was primarily regulated by abiotic processes in area with AI<0.2,while the biological effect on REE circulation in soil played a more effective role in area with AI>0.3.The similar UCC normalized patterns in topsoils suggest that the REE was originated from a common source with limited influences from other sources(e.g.,atmospheric dusts and anthropogenic contribu‑tions).Our results to some extent provide evidence for climatic influence REE distribution patterns both in topsoils and subsoils across the continental‑scale transect.Our investigation gives insights into future studies on vertical REE mobility and its associated biogeochemical pathways.展开更多
Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic a...Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic and infectious,which become a major public health hazard that has had a devastating social and economic impact worldwide(Li Q.Q.et al.,2020).Variants of the virus have emerged that behave differently(CDC2021;Gobeil et al.,2020;Leung et al.,2021).Some of them show increased infectivity(Li Q.et al.,2020;Zhang et al.,2020)and may escape from neutralizing antibodies(Weisblum et al.,2020).展开更多
基金supported by the Natural Science Foundation of Shanghai (21ZR1475600)Science and Technology Commission of Shanghai Municipality (20431900100)+4 种基金Shanghai Science and Technology Committee (19430750100)National Key R&D Program of China (2016YFA0502301 and 2021YFC2301204)Drug development for the newly emerging viral infectious diseases (SIMM010107)Fundamental Research Funds for the Central Universities (2022ZFJH003)Zhejiang Provincial Key Research&Development Program of China (2021C03043 and No.2021C03039).
文摘Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.
基金supported by the National Key Research&Development Program of China(No.2021YFC2301204)Zhejiang Provincial Key Research&Development Program of China(No.2021C03043)Research Project of Jinan Microecological Biomedicine Shandong Laboratory.
文摘Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person.We need to revisit this virus to prevent the epidemic from getting worse.In this review,we comprehensively summarize studies on monkeypox,including its epidemiology,biological characteristics,pathogenesis,and clinical characteristics,as well as therapeutics and vaccines,highlighting its unusual outbreak attributed to the transformation of transmission.We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.
基金supported by Chinese Academy of Sciences(No.E01X0301)National Natural Science Foundation of China(Grant No.41673005)support from China Scholarship Council.Youth Innovation Promotion Association CAS to Chao Wang(2018231).
文摘Background:Rare earth elements(REE)are a group of trace elements that behave geochemically coherently.REE fractionation patterns normalized to reference materials provide a powerful tool for documenting pedogenesis.Insoil processes are particularly difficult to illustrate with respect to contemporary and past climate conditions.In this study,we characterize the rare earth element(REE)contents in bulk soils and respective geochemical fractions(e.g.,exchangeable,carbonate‑bound,reducible,and oxidizable fractions)and to decipher the relationships between REE geochemistry components and climatic factors across a large‑scale northern China transect(NCT).Results:Across the NCT,bulk REE concentrations ranged from 55.2 to 241.1μg g^(−1)with a main portion in the residual fraction(49–79%),followed by oxidizable fraction(2–40%),reducible fraction(3–22%),carbonate‑bound fraction(0.1–16%),and negligible exchangeable fraction.The REE contents of geochemical components(carbonate‑bound,reducible,and oxidizable)in topsoils correlated to climate factors(mean annual precipitation,mean annual temperature,potential evaporation,and aridity index(AI)).The normalized abundances to the upper continental crust(UCC)composition show that the middle REE was generally enriched than the light REE and heavy REE in topsoils along the transect.The overall UCC‑normalized bulk REE patterns in topsoils and subsoils were similar,characterized by weak negative Ce anomalies and positive Eu anomalies.Conclusions:Our data in topsoils and depth profiles collectively suggest that cycling of REE was primarily regulated by abiotic processes in area with AI<0.2,while the biological effect on REE circulation in soil played a more effective role in area with AI>0.3.The similar UCC normalized patterns in topsoils suggest that the REE was originated from a common source with limited influences from other sources(e.g.,atmospheric dusts and anthropogenic contribu‑tions).Our results to some extent provide evidence for climatic influence REE distribution patterns both in topsoils and subsoils across the continental‑scale transect.Our investigation gives insights into future studies on vertical REE mobility and its associated biogeochemical pathways.
基金supported by the Zhejiang Provincial Key Research and Development Program(#2021C03043 and#2021C03039)。
文摘Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic and infectious,which become a major public health hazard that has had a devastating social and economic impact worldwide(Li Q.Q.et al.,2020).Variants of the virus have emerged that behave differently(CDC2021;Gobeil et al.,2020;Leung et al.,2021).Some of them show increased infectivity(Li Q.et al.,2020;Zhang et al.,2020)and may escape from neutralizing antibodies(Weisblum et al.,2020).
