Traditional Chinese medicine in antiviral treatment

Hua Wang,Qin Wang＊,Jia-Yu Chen,Guo-Juan Shi,Lin-Wei Chen＊

1Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine,Taizhou 225300,China.

Abstract

Keywords:Traditional Chinese medicine,Antiviral treatment,Mechanism,Research status,Prospect

Background

Novel Coronavirus (COVID-19) broke out in Wuhan,China in December 2019,followed by a global outbreak.The COVID-19 has a high disease rate,high pathogenicity and high susceptibility to drug resistance,making antiviral strategies a major scientific issue facing human [1-2].At present,the antiviral drugs are few,the effect is not ideal,and the development of antiviral drugs requires a huge investment; meanwhile,vaccine development obviously lags behind,which will make antiviral efforts uncontrollable.

Traditional Chinese medicine (TCM) regards infectious diseases caused by viruses as“plagues”,and TCM has played an important role in the fight against various “epidemics” (infectious diseases) encountered for thousands of years [3-4].Especially since 2003,TCM has played an effective role in fighting against viral diseases such as against severe acute respiratory syndrome,H1N1 influenza,H7N9 flu virus,middle east respiratory syndrome and Ebola virus infection[5-6].In this paper,the classification,mechanism,existing problems and the prospect of traditional Chinese medicine in antiviral treatment has been summarized in order to provide certain reference for the research and prescription screening of traditional Chinese medicine anti-COVID-19 drugs.

Classification of antiviral TCM

According to different antiviral efficacies,TCM herbs can be divided into Qing Re (clearing heat) herbs,Jie Biao (relieving exterior syndrome) herbs,Bu Xu(curing deficiency) herbs and Huoxue Huayu(invigorate the circulation of blood) herbs,etc.,as shown in Table1 [7,8].The Qing re herbs have the functions of clear internal heat,discharging fire,and relieving internal heat or fever,which mainly includes Lianqiao (Forsythiae Fructus),Huangqin (Scutellariae Radix),Chishao (Paeoniae Radix Rubra),Huangbai(Phellodendri Chinensis Cortex),etc.The antiviral active ingredients are mainly alkaloids,glycosides,etc.,and their antiviral mechanisms are mostly direct-action pathways that inhibit viral adsorption,replication,etc.The Jie biao herbs generally refer to the different degrees of sweating,antipyretic,antiviral,diuretic and other effects,viral diseases such as rubella,influenza and other initial onset,all external symptoms are urgent.Mahuang (Ephedrae Herba),Guizhi(Cmnamomi Mmulus),Xixin (AsariRadix Et Rhizoma),Jingjie (Schizonepetae Herba),etc are this kind of herbs.The antiviral active components are essential oil,glycosides,etc,and their antiviral mechanisms includes the direct effect of inhibiting virus penetration,adsorption,replication,and the indirect effect of regulating interferon and cytokine.Bu xu herbs are a kind of TCM which has the effect of supporting vital energy to dispel pathogenic factors.It can enhance the immune function of the body and produce the effect of supporting vital energy and dispelling pathogenic factors.It mainly includes Huangqi (Astmgali Radix),Renshen (Ginseng Radix Et Rhizoma),Gancao (Radix Rhizoma Glycyrrhizae),Baizhu (Macrocephalae Rhizoma),etc.The antiviral active components mainly include glycosides,polysaccharides,flavonoids,etc.and antiviral mechanism includes the direct effect of inhibiting virus replication,and the indirect effect of regulating the immune function of the body such as cytokines.Huoxue Huayu herbs can promote the recovery of pathological changes,improve metabolic function,reduce inflammation and adjust immunity.The application of Huoxue Huayu herbs is helpful to remove pathological products and ensure the normal operation ofQiand blood in the body.The TCM for Huoxue Huayu herbs mainly include Danshen(Salviae Miltiorrhizae),Niuxi (Radix Achyranthis Bidentatae),Daji(Cirsii Japonici Herba Carbonisata),Chuanxiong(Ligusticum chuanxiong Hort)and so on.Xie xia herbs is a kind of TCM with antibacterial,anti-inflammatory and enhancing the collective immune function,which often has both purgative and purgative functions.It mainly includes Dahuang (Rhei Radix Et Rhizoma),Luhui (Aloe),Shanglu (Phytolaccae Radix),Gansui(Kansui Radix),etc.,and its antiviral mechanism is the directly inhibitory effect against virus'replication.

Antiviral mechanism of TCM

The mechanisms of TCM antiviral treatment can be divided into two ways:direct antiviral and indirect antiviral.Some herbs have direct inhibition or damage effects on virus; while,some herbs can strengthen immune function.TCM has many ways to resist virus,the key to controlling virus infection lies in giving play to the body's restrictive mechanism and inhibiting virus replication[9-13](Table2).

Direct antiviral pathway

The direct antiviral treatments play direct roles in all aspects of virus proliferation.The process of virus proliferation can be roughly divided into adsorption,penetration,uncoating,genome transcription,genome replication and gene expression,assembly,maturation and release (Figure 1).The direct antiviral effects around it can be divided into the following categories:(1) Inhibiting virus adsorption and invasion.The cell membrane is the first barrier for viruses to enter the cell.Adsorption and invasion are when the virus attaches to the surface of susceptible cells and then the viral nucleic acid or infectious nucleocapsid crosses the membrane and enters the cytoplasm,which is the initial stage of infection.Flavonoids,triterpenes,polysaccharides and their derivatives can inhibit the absorption of virus.(2) Inhibiting virus replication.Because nucleic acid is the genetic material of viruses,viruses can be divided into DNA viruses and RNA viruses according to different genetic materials.Preventing viral nucleic acid replication is an effective target of antiviral drugs.(3) Inhibiting virus assembly and release.The assembly and release of the virus is the last step of virus replication.Mature virus particles are released from host cells by exocytosis and budding,and there are few reports of TCM acting at this stage.

Table1 Classification of antiviral TCM

Table1 Classification of antiviral TCM(continued)

Indirect antiviral pathway

This approach mainly refers to indirectly play the role of anti-virus by enhancing the immunity and stimulating the immune defense system.The direct antiviral effects around it can be divided into the following categories:(1) Promoting the development of immune organs.Immune organ is the organization that produces immune response and performs immune function.The quality of immune organ is closely related to immune function.(2) Enhancing the role of immune cells.TCM immune enhancer can act on thymic lymphatic system,induce T cell differentiation and proliferation,form effector cells,and produce lymphoid factors.(3) Enhancing humoral immunity.The main factor of antiviral humoral immunity is antibody.The secreted IgA can prevent the local invasion of the virus,and IgG and IgM can interrupt the already invaded virus to spread through blood circulation.(4) Enhancing the phagocytosis of macrophages and the killing effect of NK cells.(5)Induced interferon.Interferon is an inducible protein controlled by the cell genome.It has a variety of biological activities such as anti-virus reproduction and tumor growth.It is a kind of defensive substance produced by oneself inside organism to resist foreign virus invasion and maintain organism or cell function self-stable.(6) Comprehensive regulation of various cytokines.Natural killer cells (NK),interferon-1(IFN-1)and interleukin-2 (IL-2) interact in the body to form an immune network and enhance antiviral and immunomodulatory effects.

Table2 Mechanism of antiviral action by multiple pathways of TCM

Figure1 Major steps in the generalized viral life cycle.A:Targets for entry inhibitors (Astmgali Radix,Scutellariae Radix,Codonopsis Radix),B:Targets for replication inhibitors(Coptidis Rhizoma,Scutellariae Radix,Rehmanniae Radix),C:Targets for cellular factors(Forsythiae Fructus,Radix Bupleuri,Cmnamomi Mmulus),D:Targets in assembly and egress(Digitalis,Phmllanthi Fructus,Laggera pterodonta).

Problems in antiviral research of TCM

At present,some achievements have been made in antiviral research of TCM,but there are still some problems as follows.(1) Antiviral researches of TCM mainly focus on single herb,antiviral spectrum and mechanism of action of TCM.Most of them are laboratory researches,and lack of syndrome basis and standardized animal model of disease and syndrome combination,which makes antiviral researches of TCM divorced from clinical practice of TCM.(2) The lack of guidance from the corresponding TCM prescription theory in the treatment of diseases caused by viral diseases restricts the rapid development of antiviral research in TCM.(3) The lack of in-depth anti-virus research on integrated Chinese and Western medicine makes it difficult to achieve new breakthroughs and restrict its development.(4) The research technology and methods are not advanced enough,and there is a lack of systematic screening system for antiviral TCM.

Research prospects

In view of the current anti-virus research of TCM,the following aspects should be implemented.(1) It is necessary to adhere to the theory of TCM,but also to integrate the latest researches of modern biological science.(2) Establishing the diagnosis and treatment system of “combination of syndrome and disease”,give full play to the advantages and characteristics of TCM.(3) Through artificial intelligence-assisted design,the selection system of TCM for antiviral should be established,and the classical prescriptions with potential antiviral effects should be vigorously explored.(4) The research on antiviral of TCM must reasonably introduce modern bioscience,promote the modernization of TCM by using the latest technologies,such as genomics,proteomics,metabolomics,immunology and other technologies.