In the realm of drug discovery,recent advancements have paved the way for innovative approaches and methodologies.This comprehensive review encapsulates six distinct yet interrelated mini-reviews,each shedding light o...In the realm of drug discovery,recent advancements have paved the way for innovative approaches and methodologies.This comprehensive review encapsulates six distinct yet interrelated mini-reviews,each shedding light on novel strategies in drug development.(a)The resurgence of covalent drugs is highlighted,focusing on the targeted covalent inhibitors(TCIs)and their role in enhancing selectivity and affinity.(b)The potential of the quantum mechanics-based computational aid drug design(CADD)tool,Cov_DOX,is introduced for predicting protein-covalent ligand binding structures and affinities.(c)The scaffolding function of proteins is proposed as a new avenue for drug design,with a focus on modulating protein-protein interactions through small molecules and proteolysis targeting chimeras(PROTACs).(d)The concept of pro-PROTACs is explored as a promising strategy for cancer therapy,combining the principles of prodrugs and PROTACs to enhance specificity and reduce toxicity.(e)The design of prodrugs through carbon-carbon bond cleavage is discussed,offering a new perspective for the activation of drugs with limited modifiable functional groups.(f)The targeting of programmed cell death pathways in cancer therapies with small molecules is reviewed,emphasizing the induction of autophagy-dependent cell death,ferroptosis,and cuproptosis.These insights collectively contribute to a deeper understanding of the dynamic landscape of drug discovery.展开更多
Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV...Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.展开更多
Oral antiretroviral drugs have been a fundamental component of human immunodeficiency virus(HIV)treatment for over three decades,and their continuously improving safety and efficacy have directly contributed to revers...Oral antiretroviral drugs have been a fundamental component of human immunodeficiency virus(HIV)treatment for over three decades,and their continuously improving safety and efficacy have directly contributed to reversing the initially devastating course of the HIV epidemic.Long-acting antiretroviral(ARV)regimens are necessary to sustain viral suppression in people living with HIV who express a strong desire to alleviate pill fatigue or avoid the potential stigma associated with daily oral regimens.The development of innovative long-acting ARVs remains an unmet requirement in the fields of HIV treatment and prevention.In this review,we provide an overview of lenacapavir,a first-in-class picomolar long-acting capsid inhibitor for HIV-1 that operates through multiple stages without any known cross-resistance to other existing antiretroviral drug classes.展开更多
Despite the availability of effective antibacterial drugs,the increasing prevalence of antibiotic-resistant bacteria is primarily attributed to their excessive and inappropriate utilization.Antimicrobial resistance(AM...Despite the availability of effective antibacterial drugs,the increasing prevalence of antibiotic-resistant bacteria is primarily attributed to their excessive and inappropriate utilization.Antimicrobial resistance(AMR)represents one of the most concerning global health and development threats[1].Thereby,the continuous escalation in AMR necessitates urgent advancements in novel antibacterial strategies.The MraY enzyme,which plays a pivotal role in synthesizing bacterial cell wall-composing polysaccharides,holds significant potential as a target for antibacterial agents[2].However,its conformational dynamics have presented substantial challenges in developing MraY-targeting inhibitors.展开更多
Drug resistance poses an escalating global challenge in the battle against infections.The effectiveness of conventional antibiotics and other anti-infective drugs is waning as microbes develop heightened resistance to...Drug resistance poses an escalating global challenge in the battle against infections.The effectiveness of conventional antibiotics and other anti-infective drugs is waning as microbes develop heightened resistance to existing treatments.Antimicrobial resistance poses a formidable challenge to global health and development,ranking among the top 10 public health threats to humanity as declared by the World Health Organization.Projections indicate that if left unaddressed,antimicrobial resistance could inflict an annual economic burden on the global GDP ranging from$1trillion to$3.4 trillion by 2030.Consequently,the management of common infections becomes increasingly arduous,while the likelihood of disease transmission,severe illness,and mortality escalates.展开更多
近年来留学生教育已成为我国高等医学教育的重要组成部分。本文在总结笔者多年对全科医学学士教育(Bachelor of Medicine and Bachelor of Surgery,MBBS)无机化学全英语教学工作的基础上,根据MBBS留学生特点,从教学内容选择、教学方式...近年来留学生教育已成为我国高等医学教育的重要组成部分。本文在总结笔者多年对全科医学学士教育(Bachelor of Medicine and Bachelor of Surgery,MBBS)无机化学全英语教学工作的基础上,根据MBBS留学生特点,从教学内容选择、教学方式的改革等方面对无机全英文教学进行了探讨,以期逐步提高教学质量。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82273770)the Foundation for Innovative Research Groups of the National Natural Science Foundation of Sichuan Province(No.24NSFTD0051).
文摘In the realm of drug discovery,recent advancements have paved the way for innovative approaches and methodologies.This comprehensive review encapsulates six distinct yet interrelated mini-reviews,each shedding light on novel strategies in drug development.(a)The resurgence of covalent drugs is highlighted,focusing on the targeted covalent inhibitors(TCIs)and their role in enhancing selectivity and affinity.(b)The potential of the quantum mechanics-based computational aid drug design(CADD)tool,Cov_DOX,is introduced for predicting protein-covalent ligand binding structures and affinities.(c)The scaffolding function of proteins is proposed as a new avenue for drug design,with a focus on modulating protein-protein interactions through small molecules and proteolysis targeting chimeras(PROTACs).(d)The concept of pro-PROTACs is explored as a promising strategy for cancer therapy,combining the principles of prodrugs and PROTACs to enhance specificity and reduce toxicity.(e)The design of prodrugs through carbon-carbon bond cleavage is discussed,offering a new perspective for the activation of drugs with limited modifiable functional groups.(f)The targeting of programmed cell death pathways in cancer therapies with small molecules is reviewed,emphasizing the induction of autophagy-dependent cell death,ferroptosis,and cuproptosis.These insights collectively contribute to a deeper understanding of the dynamic landscape of drug discovery.
基金supported by the Key Research and Development Program,Ministry of Science and Technology of the People’s Republic of China(Nos.2023YFC2606500,2023YFE0206500).
文摘Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.
基金supported by National Key R&D Program of China(No.2023YFC2306800)Natural Science Foundation of Shandong Province(No.ZR2024QH201)+4 种基金the Postdoctoral Fellowship Program of CPSF(No.GZC20231489)China Postdoctoral Science Foundation(No.2023M742101)the Key Research and Development Program,Ministry of Science and Technology of the People’s Republic of China(No.2023YFC2606500)the Shandong Laboratory Program(No.SYS202205)Sanming Project of Medicine in Shenzhen(No.SZSM202311032).
文摘Oral antiretroviral drugs have been a fundamental component of human immunodeficiency virus(HIV)treatment for over three decades,and their continuously improving safety and efficacy have directly contributed to reversing the initially devastating course of the HIV epidemic.Long-acting antiretroviral(ARV)regimens are necessary to sustain viral suppression in people living with HIV who express a strong desire to alleviate pill fatigue or avoid the potential stigma associated with daily oral regimens.The development of innovative long-acting ARVs remains an unmet requirement in the fields of HIV treatment and prevention.In this review,we provide an overview of lenacapavir,a first-in-class picomolar long-acting capsid inhibitor for HIV-1 that operates through multiple stages without any known cross-resistance to other existing antiretroviral drug classes.
文摘Despite the availability of effective antibacterial drugs,the increasing prevalence of antibiotic-resistant bacteria is primarily attributed to their excessive and inappropriate utilization.Antimicrobial resistance(AMR)represents one of the most concerning global health and development threats[1].Thereby,the continuous escalation in AMR necessitates urgent advancements in novel antibacterial strategies.The MraY enzyme,which plays a pivotal role in synthesizing bacterial cell wall-composing polysaccharides,holds significant potential as a target for antibacterial agents[2].However,its conformational dynamics have presented substantial challenges in developing MraY-targeting inhibitors.
文摘Drug resistance poses an escalating global challenge in the battle against infections.The effectiveness of conventional antibiotics and other anti-infective drugs is waning as microbes develop heightened resistance to existing treatments.Antimicrobial resistance poses a formidable challenge to global health and development,ranking among the top 10 public health threats to humanity as declared by the World Health Organization.Projections indicate that if left unaddressed,antimicrobial resistance could inflict an annual economic burden on the global GDP ranging from$1trillion to$3.4 trillion by 2030.Consequently,the management of common infections becomes increasingly arduous,while the likelihood of disease transmission,severe illness,and mortality escalates.
文摘近年来留学生教育已成为我国高等医学教育的重要组成部分。本文在总结笔者多年对全科医学学士教育(Bachelor of Medicine and Bachelor of Surgery,MBBS)无机化学全英语教学工作的基础上,根据MBBS留学生特点,从教学内容选择、教学方式的改革等方面对无机全英文教学进行了探讨,以期逐步提高教学质量。
