Classification of commonly used antiviral drugs?
Viruses include DNA virus and RNA virus . After virus infection, its replication cycle is divided into five steps: adsorption penetration, dehulling replication, biosynthesis, assembly maturation and release. The role of antiviral drugs is achieved by competing for cell surface receptors, preventing virus adsorption, hindering virus penetration and dehulling, inhibiting virus synthesis, enhancing host antiviral ability, blocking assembly maturation and other links. Generally speaking, antiviral drugs mainly include broad-spectrum antiviral drugs , anti-DNA viral drugs , anti-RNA viral drugs , protease inhibitor antiviral drugs and inhibit RNA synthesis antiviral drugs (see Table 3 for the classification and mechanism of common antiviral drugs).
Recommended Opinions 7: Commonly used broad-spectrum antiviral drugs include interferon, ribavirin and abidol, anti-DNA virus drugs include ganciclovir , etc. Anti-RNA virus drugs include M2 ion channel blocker adamantane, neuraminidase inhibition oseltamivir, and protease inhibitor lopinavir/ ritonavir , etc. The specific antiviral drug treatment should be based on the pathogenesis, body conditions and drug resistance.
Empiric antiviral treatment strategy for acute respiratory virus infection in adults?
Acute respiratory virus infection is generally self-limiting. For example, the patient is upper respiratory tract infection and the suspected pathogen is rhinovirus , etc. People with mild symptoms mainly use symptoms to relieve symptoms and support treatment, and antiviral drugs may not be given. For patients with severe symptoms, prolonged course of disease, severe lower respiratory tract infection of , or high-risk groups, empirical antiviral treatment should be given based on the most likely pathogenic virus or POCT results. However, there is currently a lack of evidence-based medical literature on drug treatment after non-communicable acute respiratory virus infection. Existing literature shows that there are no specific antiviral drugs for rhinovirus, adenovirus , human parainfluenza virus, human metapneumovirus, human Boca virus, enterovirus, etc. After respiratory syncytial virus is infected with , ribavirin showed a certain effect. The US FDA approved atomized inhalation ribavirin for the treatment of lower respiratory syncytial virus infection in children, but it is not approved for the treatment of lower respiratory infection in adults. Multiple single-center studies believe that ribavirin early after respiratory syncytial virus infection in patients with organ transplantation or immunosuppressed state can effectively prevent the progress of upper respiratory tract infection toward downward respiratory infection . In the 2019 American Transplant Association Committee Guidelines for Infectious Diseases, ribavirin is recommended for the treatment of upper or lower respiratory syncytial virus infection after lung transplantation (weak recommendation, moderate-quality evidence level), and ribavirin is recommended for the treatment of lower respiratory syncytial virus infection after non-pulmonary solid organ transplantation (weak recommendation, low-quality evidence level), but high-quality evidence-based medical evidence is still lacking.
Recommendation 8: For respiratory virus infections in non-high-risk populations, routine antiviral drugs are not recommended; however, for respiratory syncytial virus infections in high-risk populations, ribavirin antiviral drugs are recommended in the early stage of treatment.
Antiviral treatment strategies for common infectious acute respiratory virus infection?
Human influenza virus is a single-stranded negative-strand RNA virus, which is divided into four types: A, B, C and D according to nuclear protein and matrix protein. influenza virus is prone to mutation. The mutation mainly comes from the mutation of hemagglutinin (HA) and neuraminidase (NA). Based on the different antigen characteristics of HA and NA, influenza A is divided into 18 H subtypes (H1-H18) and 11 N subtypes (N1-N11). The forms of influenza virus mutation are mainly antigen drift and antigen conversion.People are generally susceptible to influenza viruses. In October of each year, all parts of my country have entered the winter and spring epidemic season of influenza . The "Influenza Diagnosis and Treatment Plan 2020 Edition" released by National Health Commission recommends that anti-influenza virus treatment should be given as soon as possible. Neuraminidase inhibitors (including oseltamivir , zanamivir and paramivir ) are effective against influenza A and B viruses. The hemagglutinin inhibitor abidol can also be used for the treatment of influenza A and B.
Avian influenza virus (AIV) structure is similar to other influenza A virus . It is a single-stranded negative-strand RNA virus. According to the virulence of AIV on chickens, it is divided into low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI). avian influenza virus can mediate the production of various cytokines in respiratory mucosal epithelial cells and immune cells (such as IL-6, TNF-α, IL-8, IL-10, INF-α, INF-γ and CCL-2, etc.), causing " cytokine storm ". The National Health Commission issued the "Human Avian Influenza Diagnosis and Treatment Plan" and "Human Avian Influenza Diagnosis and Treatment Plan" and "Human H7N9 Influenza Infection (First Edition, 2017)": Antiviral drugs should be used as early as possible without waiting for pathogenic test results. The recommended drugs are neuraminidase inhibitors (including oseltamivir, zanamivir and paramivir). SARS-CoV is a subgroup of β-B coronavirus, which is transmitted from close to respiratory droplets. It is the main way of respiratory transmission of SARS and the most important way of SARS transmission. After infection, it leads to infectious atypical pneumonia ( severe acute respiratory syndrome , SARS). From 2002 to 2003, SARS spread worldwide. SARS-CoV The receptor that enters the cell is ACE2, which is mainly present in the lower respiratory tract. The clinical manifestations of SARS are mainly influenza-like symptoms , including fever exceeding 38 ℃, myalgia, dyspnea, and often no upper respiratory tract catalactia symptoms, and chest X-ray infiltration. The "Diagnosis and Treatment Plan for Infectious SARS (2004 Edition)" released by the National Health Commission and the latest literature show that no specific drugs for SARS-CoV have been found. The efficacy of protease inhibitor drugs ropinavir and ritonavir remains to be verified. The novel coronavirus (SARS-CoV-2) belongs to the β-genus coronavirus, has envelopes, and the particles are round or oval. They are often polymorphic and have a diameter of 60~140nm. Their genetic characteristics are significantly different from those of SARSr-CoV and MERSr-CoV. In its genome of about 30 kb, only 10 kb is the coding region , encoding structural proteins and auxiliary proteins. The structural proteins they encode are: spike protein (S), membrane protein (M), envelope protein (E) and nucleocapsid protein (N). Among them, the S protein can be cleaved by the host protease into two subunits S1 and S2. The S1 subunit is located at the apex of the envelope spike, mediating the binding of the virus to the viral receptor on the surface of the host cell, and is the key protein that determines the invasion of the virus to susceptible cells. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2) in humans. The source of infection is mainly confirmed patients, and the asymptomatic infection of may also become a source of infection. Trans-respiratory droplet transmission and close contact are the main transmission routes, and people are generally susceptible. After infection, fever, dry cough and fatigue are the main manifestations. Most patients have a good prognosis of and , and the prognosis of elderly people and those with chronic underlying diseases is poor. Iran A prospective randomized controlled study showed that patients with COVID-19 can benefit from Abidol treatment. The "Diagnosis and Treatment Plan for the New Coronavirus Pneumonia (Trial Eighth Edition)" issued by the National Health Commission: α-interferon, chloroquine phosphate, ribavirin and abidor may have certain therapeutic effects, but it is not recommended to use 3 or more antiviral drugs at the same time.
Recommended Opinions 9:
(1) For SARS-CoV, no specific therapeutic drugs have been found, lopinavir/ritonavir can be considered;
(2) For human infection with highly pathogenic avian influenza, especially H1 (H1N.), HA(HAN.) For H9N9 series of viruses, the neuraminidase inhibitor paramivir can be selected;
(3) For adult influenza A and B, the neuraminidase inhibitor oseltamivir, zanamivir, paramivir and hemagglutinin inhibitor abidol;
(4) For new coronavirus pneumonia , the neuraminidase inhibitors: α-interferon, chloroquine phosphate, ribavirin and abidol, etc., but it is not recommended to use 3 or more antiviral drugs at the same time. How to reasonably use broad-spectrum antiviral drugs in
?
Ribavirin is a broad-spectrum antiviral drug of nucleosides. The phosphorylation product of ribavirin in the body can inhibit inosine monophosphate dehydrogenase, influenza virus mRNA polymerase and mRNA guanosine transferase, causing the reduction of guanosine triphosphate in the cell, impairing the synthesis of viral RNA and protein , thereby hindering the replication and spread of the virus. Ribavirin can pass through the blood-cerebrospinal fluid barrier, and the concentration of drugs in respiratory secretions is mostly higher than that in blood drug concentrations. It can pass through the placenta and enter milk. It is metabolized in the liver and is mainly excreted through the kidneys. The drugs accumulate in red blood cells in for several weeks, and the half-life of elimination can reach 40 days. Ribavirin has a definite antiviral efficacy, but it is generally necessary to combine other antiviral drugs, and oseltamivir is the most common drug used in combination. The most common adverse reactions of ribavirin are hemolytic anemia . When using it, the patient's liver and renal functions should be monitored and the dosage should be adjusted in time.
Currently, commonly used interferons in clinical practice include common interferon α (IFNα) and polyethylene glycol interferon α. IFNα can regulate the viral transcription and translation process, improve the body's immune effector activity, induce cell transport between antiviral functional molecules, and thus achieve the function of inhibiting many different RNA and DNA viruses. Interferon can effectively inhibit respiratory syncytial virus , influenza virus, herpes virus , etc. In vitro experiments have also shown that it can inhibit the proliferation of MERS-CoV. Interferon is mainly metabolized by the kidneys, and the half-life of is 2~8 hours, and is mostly degraded in the body. Interferon can be used to treat MERS, SARS, and COVID-19 (recommended air compression or oxygen discharging method). The main adverse reactions or adverse reactions of include: influenza-like syndromes produced when combined with ribavirin, myelosuppression, mental abnormalities, inducing autoimmune diseases , shortness of breath and dry cough, etc., which are prone to causing central nervous system , heart and systemic adverse reactions in the elderly.
Abidol is a non-nucleoside broad-spectrum antiviral drug with immune enhancement effect. It is the only hemagglutinin inhibitor. Abidol can hinder the fusion of viruses and cell membranes, the invasion of viruses, the replication and maturation of viruses and the immune regulation mechanisms to exert antiviral effects. This drug is approved in China for the treatment of upper respiratory tract infections caused by influenza A and B viruses. In vitro experiments have shown inhibitory activities on a variety of viruses, including most enveloped viruses and a few non-encapsulated viruses, such as rhinovirus, adenovirus, respiratory syncytial virus, coxsackie virus, coronavirus (including SARS-CoV-2), etc. The "Diagnosis and Treatment Plan for the New Coronavirus Pneumonia" formulated by the National Health Commission recommends the use of Abidol. Abidol is mainly metabolized by the liver in the human body and has good tolerance and safety in the human body. The incidence of adverse reactions of Abidol is about 6.2%, mainly manifested as nausea, diarrhea, dizziness, increased serum aminotransferase, occasional adverse events such as increased bilirubin, numbness, decreased platelets, and decreased leukocytes.
Recommended Opinions 10: Ribavirin has a definite antiviral efficacy, but generally requires the use of oseltamivir and other drugs; interferon is mainly used for respiratory syncytial virus, influenza virus, herpes virus and other infections; abidol can be used for influenza A and B viruses, novel coronaviruses and other respiratory viruses. What are the main drug resistance problems of
?
Viruses are composed of only DNA or RNA because of their simple structure. During the replication of the virus, base mutations are prone to occur and pathogenic gene mutations. This structural change is more common in RNA viruses. Two different viral strains form new viral strains through antigen drift or gene rearrangement. The single nucleotide polymorphism of viral RNA (SNP) may exist both in the virus itself and in its target sequence. For example, influenza viruses can cause small mutations of antigens through antigen drift, but no new subtypes will be produced. Antigen conversion will produce strong pathogenic strains due to excessive changes in the encoding gene, resulting in ineffective human protoimmunity. Avian influenza viruses also produce new mutations through antigen drift and lead to reduced antibody response to inoculated avians. Therefore, viruses are very prone to drug resistance, and existing commonly used antiviral drugs such as ribavirin, adamantadine, oseltamivir, etc. all have certain drug resistance. However, the current research on viral resistance is mostly focused on viral hepatitis and acquired immunodeficiency syndrome (AIDS), while research on respiratory virus resistance is mainly focused on influenza virus resistance. At present, the M2 ion channel blockers adamantane and adamantine are not recommended for the treatment of influenza A due to their high resistance to influenza A virus. Neuraminidase inhibition (NAI) oseltamivir is not common in influenza A and B viruses (1% to 3%), but is elevated in critically ill patients and in immunocompromised patients. The detection of WHO found that the vast majority of influenza viruses (99%) were sensitive to all four NAIs (oseltamivir, zanamivir, paramivir, and lanimvir), and NAI is still the recommended antiviral drug for treating influenza virus infection with .
Recommended Opinions 11: Antiviral drugs' resistance to respiratory viruses is mainly concentrated in influenza viruses. WHO still recommends neuraminidase inhibition (NAI) as the first choice drug for the treatment of influenza virus infection.
The timing and course of treatment of antiviral drugs?
The incubation period after the virus invades the respiratory tract is generally 48h (range: 24~96h). After 24~72h invades the respiratory tract, the virus begins to reach the peak of detoxification. Drug intervention within 48h can inhibit virus reproduction, reduce inflammatory reactions, and reduce damage to other tissues and organs. It can significantly shorten the course of the disease or reduce the incidence of complications. However, after 48h onset, the course of the disease will be shortened by up to 1 day. The virus generally continues to detoxify in human respiratory secretions for 3 to 7 days, and the average detoxification time is 4.5 days. If the influenza virus invades the respiratory tract for 6 to 10 days, the secretions cannot be detected. The normal human adaptive immune response can last for 5 to 14 days, and the production of antibodies is generally produced 1 to 2 weeks after the virus infection. Therefore, the course of the disease after respiratory virus infection is generally within 7 to 10 days.
