ABSTRACT
Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the Food and Drug Administration are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These recommended antivirals are currently effective for major subtypes of IVs as the compounds target conserved domains in neuraminidase or polymerase acidic (PA) protein. However, this trend may gradually change due to the selection of antiviral drugs and the natural evolution of IVs. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.
Subject(s)
Antiviral Agents , Clinical Trials as Topic , Drug Development , Influenza, Human , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Influenza, Human/drug therapy , Influenza, Human/virology , Orthomyxoviridae/drug effects , Zanamivir/pharmacology , Zanamivir/therapeutic use , Dibenzothiepins , Morpholines , Pyridones , TriazinesABSTRACT
Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the FDA are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. Notably, owing to the high variability of IVs, no drug exists that can effectively treat all types and subtypes of IVs. Moreover, the current trend of drug resistance is likely to continue as the viral genome is constantly mutating. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.
Subject(s)
Influenza, Human , Orthomyxoviridae , Humans , Influenza, Human/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Oseltamivir/therapeutic use , Zanamivir/therapeutic use , Drug Resistance, Viral/genetics , Neuraminidase/genetics , Enzyme Inhibitors/pharmacologyABSTRACT
The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.
ABSTRACT
The outbreaks of severe acute respiratory syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV and SARS-CoV-2, respectively, have posed severe threats to global public health and the economy. Treatment and prevention of these viral diseases call for the research and development of human neutralizing monoclonal antibodies (NMAbs). Scientists have screened neutralizing antibodies using the virus receptor-binding domain (RBD) as an antigen, indicating that RBD contains multiple conformational neutralizing epitopes, which are the main structural domains for inducing neutralizing antibodies and T-cell immune responses. This review summarizes the structure and function of RBD and RBD-specific NMAbs against SARS-CoV and SARS-CoV-2 currently under development.
Subject(s)
Antibodies, Monoclonal/chemistry , Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Severe Acute Respiratory Syndrome/prevention & control , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal/biosynthesis , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cross Reactions , Epitopes/chemistry , Epitopes/immunology , Epitopes/metabolism , Humans , Models, Molecular , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/immunology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Protein Binding , Protein Structure, Secondary , Receptors, Virus/chemistry , Receptors, Virus/immunology , Receptors, Virus/metabolism , Severe acute respiratory syndrome-related coronavirus/drug effects , Severe acute respiratory syndrome-related coronavirus/immunology , Severe acute respiratory syndrome-related coronavirus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Virion/immunology , Virion/ultrastructureABSTRACT
Influenza continues to be a significant public health challenge. Two glycoproteins on the surface of influenza virus, hemagglutinin and neuraminidase, play a prominent role in the process of influenza virus infection and release. Monoclonal antibodies targeting glycoproteins can effectively prevent the spread of the virus. In this review, we summarized currently reported human monoclonal antibodies targeting glycoproteins of influenza A and B viruses.
Subject(s)
Antibodies, Monoclonal/immunology , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A virus/immunology , Influenza B virus/immunology , Neuraminidase/immunology , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Epitopes , Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Humans , Neuraminidase/chemistry , Neuraminidase/metabolism , Orthomyxoviridae Infections/therapy , Orthomyxoviridae Infections/virologyABSTRACT
Hantavirus (HV), a pathogen of animal infectious diseases that poses a threat to humans, has attracted extensive attention. Clinically, HV can cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), between which HFRS is mostly in Eurasia, and HPS is mostly in the Americas. This paper reviews the research progress of small-molecule inhibitors of HV.
Subject(s)
Antiviral Agents/pharmacology , Orthohantavirus/drug effects , Small Molecule Libraries/pharmacology , Animals , Orthohantavirus/physiology , Hantavirus Infections/virology , Host-Pathogen Interactions/drug effects , Humans , Peptides/chemistry , Peptides/pharmacology , Viral Proteins/antagonists & inhibitors , Viral Proteins/chemistry , Virus Replication/drug effectsABSTRACT
In recent years, the outbreak of infectious disease caused by Zika virus (ZIKV) has posed a major threat to global public health, calling for the development of therapeutics to treat ZIKV disease. Here, we have described the different stages of the ZIKV life cycle and summarized the latest progress in the development of small-molecule inhibitors against ZIKV infection. We have also discussed some general strategies for the discovery of small-molecule ZIKV inhibitors.
