It is often seen in daily life that if a patient has a bacterial infection, the disease is quickly cured after a few days of antibiotics. In contrast, with chronic viral infections such as hepatitis B and AIDS, doctors usually tell patients that it is difficult to clear the virus and that they need to take antiviral drugs for a long time to suppress the virus, and that there is a risk of drug resistance. Why are these viruses so stubborn? Why are antiviral drugs so ineffective? In this article, we will introduce the intrinsic reasons from the special characteristics of virus structure and reproduction. Many antiviral drugs eliminate the virus and may also cause serious damage to the host, making drug development difficult. Bacteria have a unique cell structure, namely cell wall, cell membrane, cytoplasm, as long as the outside world has nutrients to feed themselves. Many of the anti-bacterial drugs invented by scientists target the unique cell wall, cell membrane and other cellular structures of bacteria, and destroy them by destroying these structures, thus causing little or no damage to the human body. Viruses are not as capable as bacteria. Viruses have a simple structure, no complete cellular structure, and lack a complete enzyme system, thus determining their specialized parasitism. The virus must invade a susceptible host cell, rely on the host cell’s enzyme system, raw materials and energy to replicate the viral nucleic acid, and translate the viral protein with the help of the host cell’s ribosome in order to reproduce. Many drugs therefore destroy viruses while causing significant damage to the body. Although some drugs have strong antiviral effects, they cannot be used clinically because of their serious toxic side effects. The development of low-toxicity and high-efficiency antiviral drugs is facing great difficulties. 2, the lack of self-correcting ability of viral replication, constant mutation, resulting in mutations, resulting in the failure of drugs to inhibit viral replication. The replication of viruses in the human body is rapid, and in the case of hepatitis B virus, for example, 1012 to 1013 new viral particles can be produced every day. Since the reverse transcription link is involved in the HBV replication cycle, and the reverse transcriptase of HBV lacks correction function, the mutation rate of HBV is also higher in each replication cycle of HBV, with a mismatch probability of about 1.4~3.2×10-5/year per base, and the mutation rate is about 10 times higher than that of other DNA viruses. Such high viral load and renewal rate as well as lower replication fidelity can increase the generation of mutations. In a patient with active replication of chronic hepatitis B, each base of HBV has the potential to mutate daily, and mutations in the viral genes allow the infection to persist as it evades antiviral drugs and immune cells. Thus, various types of mutated strains, including those resistant to different nucleoside (acid) analogues, may already exist prior to antiviral treatment. Also, the likelihood that a mutant strain resistant to a drug will be selected during antiviral therapy depends on the ability of that drug to inhibit the virus. Since drugs with lower antiviral activity do not exert continuous pressure on the virus, the incidence of resistance is higher; in contrast, if a drug completely inhibits the replication of the virus, the rate of resistance of the virus to this drug is also very low. Although different nucleoside (acid) analogues have different abilities to inhibit the replication of HBV, none of them can clear the virus. Theoretically, any one nucleoside (acid) analogue used alone for a long time, because only for a single target of the virus, there is the possibility of drug resistance, the difference is the difference in the time of appearance. 3, the virus in the body in a variety of forms. Take hepatitis B virus as an example, in addition to the well-known viral gene (HBV DNA) in the patient’s liver, there are other forms of viral genes: covalent closed-loop DNA (ccc DNA) hidden in the nucleus of hepatocytes, and viral DNA integrated into human chromosomes (once HBV DNA is integrated into human chromosomes, it becomes part of the human gene). Currently, all drugs are ineffective against ccc DNA and do not inhibit the replication of integrated viruses, nor do they remove these integrated viruses. Once the drugs are discontinued, they can be quickly transcribed into viral RNA, which is then translated into the full viral protein. The longer the course of the disease, the greater the chance of integration and the lower the sensitivity to drugs. The presence of multiple genetic forms of the virus is also, one of the major reasons why the virus is difficult to remove.