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
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
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
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
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
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 (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.
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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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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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.
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.
ABSTRACT
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
The epidemic caused by coronavirus poses a serious threat to human health, but there is no specific drug or vaccine for the treatment of this kind of virus infection. Herein, this article selects typical case studies in recent years and reviews the medicinal chemistry strategies of anti-SARS-CoV, MERS-CoV and other coronavirus drugs from the perspective of medicinal chemistry, and tries to provide some clues to current drug research againstSARS-CoV-2.
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West Nile virus is a flavivirus transmitted by culex mosquitoes. People are generally susceptible to it, West Nile virus infection can cause west Nile fever, which can develop West Nile viral encephalitis and even lead to death. There are currently no approved specific antiviral drugs against West Nile virus. Therefore, seeking effective West Nile virus inhibitors is a hot topic in current community of medicinal chemistry. In this article, based on the main targets of West Nile virus, we summarize the new progress research on West Nile virus inhibitors.
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Chikungunya fever (CHIKF) is an arthropod-borne infection disease caused by Chikungunya virus (CHIKV), which represents a serious health problem worldwide. There is no antiviral drugs treatment for CHIKV infections, neither is there an effective vaccine for prevention of the disease. Herein, we reviewed the recent reported and classical inhibitors of CHIKV, and summarized the medicinal chemistry strategies for discovering CHIKV inhibitors.
ABSTRACT
In recent years, enterovirus infection has become a frequent epidemic and developed into an important public health problem. For example, hand-foot-mouth disease has become a common infection among children in China. Hand-foot-mouth disease (HFMD) has been spreading globally since 1997, especially in the Asia-Pacific region. Enterovirus 71 (EV71) is one of the main pathogens causing HFMD. And now there is no drug available to treat EV71 infection. This review summarizes the research progress of anti-enterovirus-71 drugs from the perspective of medicinal chemistry.
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Poxvirus is the largest and most complex virus of the known virions, and the main pathogenicity to humans is Orthopoxvirus. In recent years, with the deep understanding of the biological structure and replication cycle of Orthopoxvirus, new small molecular compounds with high efficiency and low toxicity have been discovered as new drugs, and some have entered the clinical trial stage. This article summarizes the research progress of poxvirus inhibitors with different targets.
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Adenovirus is a common cause of infection in children and adults with acute respiratory tract, gastrointestinal tract and urinary tract. It can cause serious and even fatal infections in patients with low immune function. Therefore, it poses a great threat to human health. Currently, there are no specific anti-adenoviral drugs in market. With in-depth investigation of the pathogenic mechanism and biological characteristics of adenovirus, and the rapid development of drug screening technology, new generation of anti-adenovirus drug targets and related inhibitors have been discovered, providing new options for treatment. This review selects the representative case studies in recent years and summarizes the advances in anti-adenoviral medicinal chemistry.
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Long-term use of approved antiviral drugs can lead to drug resistance and side effects. On the other hand, there are currently no antiviral drugs or vaccines available to treat some newly emerging virus infections. Therefore, antiviral drugs research has always been a hot research topic in the field of medicinal chemistry. Natural products are an important source of antiviral drugs. This article reviews the progress of antiviral natural products discovered in the past decade to provide potential lead compounds for drug development.
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Ebola virus is extremely virulent and highly contagious. Ebola virus causes outbreaks of severe hemorrhagic fever, with human mortality rates of up to 90%. There is currently no preventive or therapeutic treatment in the form of vaccines, biological or small molecular agents. Currently, a lot of anti-Ebola virus agents have been reported. Here, we review the latest advances in this field.