ABSTRACT
Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.
ABSTRACT
The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.
ABSTRACT
Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.
ABSTRACT
COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.
ABSTRACT
As a common protease with high similarity among coronavirus species, the main protease (Mpro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.
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Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.
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Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.
ABSTRACT
Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.
ABSTRACT
To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.
ABSTRACT
From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.
ABSTRACT
Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.
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Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.
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Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.
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Objective To investigate the effects of smoking on chronic obstructive pulmonary disease(COPD) and respiratory symptoms. Methods A multi-stage, stratified cluster sampling strategy was used to select participants aged 40 or older in 5 surveillance points of Anhui Province. Questionnaires, body measurements and spirometry were used to collect data. Based on complex sampling design, Logistic regression model was conducted to analyze the effects of smoking on COPD and respiratory symptoms. Results The smokers who had smoked for ≥30 pack-years accounted for 13.9% (95% CI:10.3%-17.5%, P＜0.001) of the total population. And the smokers who had smoked for ≥40 years accounted for 8.5% (95% CI:6.7%-10.3%, P＜0.001) of the total population. On average, one smoker had smoked for 32.4 years (95% CI:31.2-33.5). Average daily cigarette consumption of daily smokers was 21.1 cigarettes (95% CI:19.6-22.7). As shown by multiple-variables Logistic regression analyses, the risk of COPD and respiratory symptoms increased with the increment of smoking pack-years and duration (all Ptrend <0.001). Conclusions Smoking was associated with COPD and respiratory symptoms. The risk of developing COPD and respiratory symptoms was greater with the increment of smoking pack-years and duration.
ABSTRACT
Hepatitis B virus (HBV) capsid protein plays an important role in the life cycle, thus becoming an ideal target for drug design. Capsid protein inhibitors can exert a synergistic antiviral effect with nucleoside drugs by inhibiting the replication of HBV. This paper reviews the research progress of capsid protein inhibitors with different structural types from the perspective of medicinal chemistry.
ABSTRACT
Hepatitis B has become one of the major diseases which seriously affect people's health and social development. Hepatitis B, with high incidence and long disease course, cannot be cured by approved drugs such as the nucleoside analogues. Therefore, the discovery of safe and efficient novel HBV inhibitors is of great significance. From the point of view of medicinal chemistry, we summarized and discussed current endeavours towards the discovery and development of anti-HBV agents of RNase H and other novel target inhibitors with various scaffolds or distinct mechanisms of action, besides the existing capsid protein inhibitors.
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At present, the most widely used anti-herpesviruses drugs are acyclovir (ACV) and its derivatives, but the emergence of herpesvirus resistance to these drugs forces people to continue to seek new anti-herpesviruses drugs. More and more new targets and inhibitors against herpesviruses have been discovered, one reason is the in-depth study of the biological characteristics and pathogenic mechanism of herpesviruses, and the other is the rapid development of new drug design and screening technology. Therefore, there are more options for the treatment of herpes infections. This review summarizes the representative achievements in the field of anti-herpesviruses drugs in recent years.
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At present, the anti-HCMV (human cytomegalovirus) drugs have some problems, such as moderate activity, poor bioavailability, which urge people to develop new anti-HCMV drugs. With the continuous study on the pathogenesis and biological characteristics of HCMV and the rapid development of new drug design strategies, new generation of anti-HCMV targets and drugs have been identified. This review selects the most representative research examples in recent years, and summarizes the new targets and research progress of anti-HCMV drugs from the perspective of medicinal chemistry.
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Respiratory syncytial virus (RSV) is the main pathogen causing respiratory infections in infants, the elderly, and immunocompromised individuals. Currently, ribavirin and the humanized monoclonal antibody palivizumab are commonly used for lower respiratory tract infections caused by RSV. However, their clinical application has been limited by their efficacy, economy and safety. Therefore, it is necessary to develop new RSV inhibitors to meet the needs of clinical prevention and treatment. This paper selects typical research cases and reviews the research progress of different target inhibitors from the perspective of medicinal chemistry.
ABSTRACT
The outbreak of the influenza viruses (IFV) caused significant harm to our health and life. Human infections caused by pathogenic avian influenza virus (AIV) have continually brought great panic and death threats to people all over the world. With the in-depth study of the biological characteristics of influenza viruses and the rapid development of drug discovery screening technology, a new generation of anti-influenza drug targets and their inhibitors have been continuously discovered, providing more options for the treatment of influenza. From the point of view of medicinal chemistry, this review summarizes and discusses current endeavours towards the discovery and development of novel inhibitors and also provides examples illustrating new methodologies that contribute to the identification of novel anti-influenza drugs.