Antiviral drugs 沈阳药科大学药物化学 教研室
Antiviral Drugs 沈阳药科大学药物化学 教研室
VIRUSES: Overview Viruses are obligate intracellular parasites, which massively multiply by diverting or "hijacking the host cell biosynthetic machinery Viruses were first defined as filterable infectious agents based on their small size and ability to cause disease (In 1892, Dr Iwanowski reported that filtered extracts of tobacco leaves with mosaic disease could still infect other plants) Viruses can range from the very small 20 nm to the near bacterial-200 200X 250 nm for the pox viruses such as vaccinia, first described by light microscopy by Dr. Buist in 1887 All classes of living organisms studied to date are the host to vIruses
VIRUSES: Overview • Viruses are obligate intracellular parasites, which massively multiply by diverting or “hijacking” the host cell biosynthetic machinery. • Viruses were first defined as filterable infectious agents, based on their small size and ability to cause disease (In 1892, Dr. Iwanowski reported that filtered extracts of tobacco leaves with mosaic disease could still infect other plants). • Viruses can range from the very small ~ 20 nm to the near bacterial – 200×200×250 nm for the pox viruses such as vaccinia, first described by light microscopy by Dr. Buist in 1887. • All classes of living organisms studied to date are the host to viruses
VIRUSES: Overview Viruses can have their own satellite viruses which borrow proteins crucial for their multiplication from the"host virus, e. g Hepatitis delta virus, which causes serious liver disease in humans already infected with Hepatitis B virus Viruses alone have very little capacity to produce anything-in the absence of the host they are usually entirely dormant (under some conditions are able to make small amounts of nucleic acid) Viruses differ from bacteria and fungi, which are usually capable of growth in the absence of host cells of other species
VIRUSES: Overview • Viruses can have their own satellite viruses, which borrow proteins crucial for their multiplication from the “host” virus, e.g. Hepatitis delta virus, which causes serious liver disease in humans already infected with Hepatitis B virus. • Viruses alone have very little capacity to produce anything – in the absence of the host they are usually entirely dormant (under some conditions are able to make small amounts of nucleic acid). • Viruses differ from bacteria and fungi, which are usually capable of growth in the absence of host cells of other species
The virus life cycle the process is initiated by binding of the virus to its particular cellular receptor The next step involves the delivery of the viral genome into the cell The method of delivery as a sophisticated"molecular hypodermic syringe"(bacteriophage of E. coll or a"molecular bomb"-goes off when the package is the appropriate host compartment
The virus life cycle • the process is initiated by binding of the virus to its particular cellular receptor. • The next step involves the delivery of the viral genome into the cell • The method of delivery as a sophisticated “molecular hypodermic syringe” (bacteriophage of E. coli) or a “molecular bomb” – goes off when the package is the appropriate host compartment
The virus life cycle Initiation phase ·1. Attachment ·2. Penetration 3. Uncoating · Replication phase 4. Gene expression 5. Genome replication Release phase 6. Assembly 7 Maturation 8. Release
The virus life cycle • Initiation phase • 1. Attachment • 2. Penetration • 3. Uncoating • Replication phase • 4. Gene expression • 5. Genome replication • Release phase • 6. Assembly • 7. Maturation • 8. Release
VIRUSES: Structure and Properties Viruses consist of particles containing a nucleic acid(RNA or DNA), Which encodes all the information necessary for multiplication in the correct environment(host) The nucleic acid constitutes the viral genome and is associated with protein to form a nucleocapsid Depending on the presence or absence of lipid in the membrane, viruses are termed enveloped or nonenveloped, respectively
VIRUSES: Structure and Properties • Viruses consist of particles containing a nucleic acid (RNA or DNA), which encodes all the information necessary for multiplication in the correct environment (host). • The nucleic acid constitutes the viral genome and is associated with protein to form a nucleocapsid. • Depending on the presence or absence of lipid in the membrane, viruses are termed enveloped or nonenveloped, respectively
Viruses: Structure Enveloped Nonenveloped Adopted from PD Minor, 2000
Viruses: Structure Enveloped Nonenveloped Adopted from PD Minor, 2000
Viruses: Structure Surface proteins Nucleocapsid Protein shel Nucleic acid Nucleic acid Lipid layer Membrane(matri rotein) Viruses contain a few proteins, lipids and nucleic acid which are accurately replicated by the infected cell to give more virus
Viruses: Structure • Viruses contain a few proteins, lipids and nucleic acid which are accurately replicated by the infected cell to give more virus
Virus Spread to other cells Cell Spread to new host Attachment to Transport to infectable Uncoating in specific cell compartment Location ell of next cell Nucleus entry 十1十 Takeover of Virus releas cell machinery Replication of genome mRNA synthesis Protein synthesis Assembly of components Assembly of particle Packaging of genome Transport to cell surface avoidance of cell death
The virus life cycle Viral genome is encased in a package composed of proteins usually encoded by the nucleic acid, and serving the functions of preserving the genome until a new host is reached, and delivering it to the right site Protecting the genome while it is in the environment-Enteroviruses such as poliovirus, are able to survive passage through the high acidity of the stomach and infect the intestine, while closely related viruses such as the rhinoviruses are not The delivery system of the virion requires the recognition of a cell as a likely target, and this frequently involves a specific interaction between the virus and a particular cell surface molecule
The virus life cycle • Viral genome is encased in a package composed of proteins usually encoded by the nucleic acid, and serving the functions of preserving the genome until a new host is reached, and delivering it to the right site. • Protecting the genome while it is in the environment – Enteroviruses, such as poliovirus, are able to survive passage through the high acidity of the stomach and infect the intestine, while closely related viruses such as the rhinoviruses are not. • The delivery system of the virion requires the recognition of a cell as a likely target, and this frequently involves a specific interaction between the virus and a particular cell surface molecule