Influenza is an acute respiratory infectious disease caused by influenza virus. Influenza virus replicate by attacking epithelial cells of host and infects more cells, which triggers the immune system to attack and destroy infected tissues of respiratory system and induces overreaction of the immune system. Some patients develop common respiratory symptoms and systemic symptoms, such as muscular stiffness, fatigue and loss of appetite. A few people also have digestive tract symptoms, such as abdominal pain and diarrhea. In severe cases, such complications as pneumonia, meningitis, acute respiratory distress syndrome and shock may appear, which may lead to multiple organ failure and even death.
Anti-influenza not only refers to inhibit virus replication, but also block the transmission of related inflammatory factors between immune cells, thus relieving excessive immune response and reducing the damage of the body caused by repairing immune response. In addition to the commonly used neuraminidase inhibitors and M2 blockers, new drugs are also being developed in other targets of virus replication and body immunity. Traditional Chinese medicine has always been known for its multi-target treatment. According to research, it was found that many active components in traditional Chinese medicine, such as quinones, flavonoids and alkaloids, are effective against influenza. In addition, the research found that the combination of Chinese and Western medicines has better anti-influenza therapeutic effect than single one of them.
Drugs inhibiting neuraminidase, a surface protein of influenza virus
The monomer of mushroom tetramer glycoprotein neuraminidase consists of stem structural domain immobilized on virus membrane and spherical head of catalytic active center. Neuraminidase cannot only cleave the glycosidic bond between hemagglutinin and sialic acid to catalyze sialic acid hydrolysis, but also expose the receptors on the cell surface by reducing the viscosity of respiratory mucus layer to enhance virus adsorption. It can also promote the spread of virus-containing tissue fluid to the lower respiratory tract to damage it in a short time. Neuraminidase is a widely developed and applied target at present.
1. Chemical drugs and small molecule compounds
Neuraminidase inhibitors (NAIs), as antiviral drugs, are widely used at present. They compete with neuraminidase (substrate) by reversibly binding with neuraminidase active sites to inhibit neuraminidase enzyme function and cut off the virus diffusion chain, thus preventing virus offspring from shedding from the host cell surface. The combination of zanamivir and neuraminidase active site E-119 forms hydrogen bond, which is designed as dry powder inhalation for local concentration in respiratory tract due to its poor bioavailability. Oseltamivir phosphate, the first oral anti-influenza western medicine, can bind to neuraminidase active site H275Y, among which R292K, E119V and H274Y are common drug-resistant mutation sites. Peramivir inhibits neuraminidase activity through the strong intermolecular interaction between its carboxyl and guanidino groups and neuraminidase active sites (including Asp151, Glu119, Glu227, etc.). R378Q, R378K and R378L are drug-resistant mutation points. Because of its poor bioavailability, it is currently the only anti-influenza drug approved by FDA for intravenous administration. Laninamivir octanoate can well inhibit the oseltamivir phosphate resistant strains, and its advantage is that it can stay in the lungs for a long time to maintain long-term inhibition. Using it once a week can effectively fight off influenza
2. Active ingredients and compound prescriptions of traditional Chinese medicine
Germacrone, a monocyclic sesquiterpene extracted from plant essential oil, can inhibit the replication and transcription of influenza virus and activity of neuraminidase in a dose-dependent manner. Combined with oseltamivir, it shows cumulative inhibition on virus infection in vivo and in vitro, representing that it has the potential to be developed alone or in combination with other drugs for the treatment of influenza. Cyanidin-3-sambubioside (C3S), a flavonoid extracted from black elderberr...
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