Pharmaceutical Microbiology

Overview of Antiviral Agents

Written by MicroDok

OVERVIEW OF ANTIVIRAL AGENTS

Antiviral agents are antimicrobial agents that specifically inhibit the replication of viruses in living cells (inclusive of human cells affected by viral particles). These antimicrobial agents like antifungal agents have poor or low selective toxicity. This is because viruses only live in living cells i.e. they are obligate intracellular parasites and cannot survive outside a living system. Because of their intracellular nature, antiviral drugs targeted at pathogenic viruses not only inhibit viral replication but they also interfere with the cellular and metabolic activities of the recipient human or animal cells. Viruses live inside their host cells; and they depend mainly on the biosynthetic and enzymatic machinery of their host cells which they overwhelm to direct their own replication processes in vivo. This is why most of the antiviral agents end up harming the recipient host aside their normal antimicrobial onslaught on their target viruses.

The number of antiviral agents like antifungal agents is very small, and this is because most drugs used for antiviral therapy also adversely affect the animal or human host taking them since the organism lives inside the cells of the recipient animal or human host. Since viruses are intracellular parasites and lives inside the host cells, most antiviral drugs target specific phases in the life cycle and/or replication processes of the viral particle while others exhibit their antimicrobial activity by targeting the nucleic acids of the viruses (either DNA or RNA) or by preventing the adherence of the viral agent to the host cells. Apart from synthetic antiviral agents used for the clinical management of some viral infections, the human body produces chemical substances that possess antiviral activity. These natural substances produced by the body and which inhibit the nefarious activities of viruses in vivo are generally known as immunomodulators.

Immunomodulators are chemical substances which boosts the body’s some components of the immune system (particularly the T-cells) in order to direct the host’s immunological response to an invading viral agent. Immunomodulators o immunomodulants can also be produced artificially, and their main function in the body is to interfere with viral replication processes in vivo i.e. inside the infected cells of living organisms. Interferon (IFN) is a typical example of an immunomodulant; and they are proteinous substances produced by viral infected cells in response to viral invasion of host cells. Interferons help to reduce the spread of viruses in the body by interfering with their replication, and they also boost the body’s response to antigenic substances (e.g. microorganisms). Interferons (IFNs) are cytokines with ability to inhibit the replicative ability of many viruses; and they are clinically relevant for treating some viral infections including those caused by the hepatitis virus and influenza virus amongst others.

Recombinant forms of IFNs also exist for clinical use, but these antiviral agents are expensive and are only used to treat a limited number of microbial infections (inclusive of viral infections). IFNs are generally produced by viral infected cells and they mainly interfere with viral mRNA during viral replication. Unlike other microorganisms (inclusive of bacteria, fungi, algae and protozoa) which contain both DNA and RNA in their genome as nucleic acids, a viral particle (virion) either contains DNA or RNA as its genetic makeup or genome. The development of viral-specific antiviral agent is complicated and difficult because drugs used for the treatment of viral infections (which are small at the moment compared to the many antibacterial agents) apart from targeting the virion also adversely leave untoward effects in the recipient host cells which harbours the viral particle. Most antiviral agents target cellular DNA in their quest for invading viral particles, and this limits the number of effective viral agents with higher selective toxicity used in clinical medicine. Despite their low selective toxicity, antiviral agents target specific sites and functions supposed to be more prevalent in the virion than in the host cell. For example, the rate at which viruses synthesize their nucleic acids (DNA or RNA) is faster compare to human or animal hosts whose cellular DNA synthesis may be slower. Viruses are fast replicating organisms and they also mutate in these processes into various forms that may be missed by antiviral agents.

CLASSIFICATION OF ANTIVIRAL AGENTS

  1. Nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs): Reverse transcriptase (RT) enzyme is an important enzyme in HIV replication. RT helps to reverse transcribe the HIV RNA into HIV proviral DNA (in a process known as reverse transcription), which can carry out the normal process of the central dogma of molecular biology (i.e. DNA-RNA-Protein). Without RT, it will be impossible for HIV to replicate in vivo; and thus the virus may not be a serious threat to humanity as it is now. Reverse transcription is usually the first thing the virus must do once it enters a host cell in order to maintain its continued perpetuation or existence in the infected host cell and elsewhere. NRTIs are antiretrovirals that target the reverse transcription step that converts the viral genomic RNA into linear double stranded DNA. Typical examples (generic name shown) include zidovudine, emtricitabine, tenofovir alafenamide, tenofovir, lamivudine and abacavir to mention a few.
  2. Non-nucleotide reverse transcriptase inhibitors (NNRTIs): NNRTIs like NTRIs target the reverse transcription step that converts the viral genomic RNA into linear double stranded DNA. Examples include (generic name shown) efavirenz, nevirapine, etravirine and rilpivirine.
  3. Protease inhibitors (PIs): Protease are other important enzymes that help to breakdown or cleave the polyproteins produced during HIV replication into their respective constituent and smaller proteins required for the formation of a new virion. Protease is critical for the maturation of viral particles that bud out from infected host cells Typical examples include (generic name shown) indinavir, ritonavir, saquinavir, tipranavir and atazanavir.
  4. Integrase inhibitors: Integrase enzyme helps the HIV genome to be successfully integrated into the genome of the infected host cell. Without this enzyme, HIV replication may not proceed further. Integrase inhibitors can also be called integrase strand transfer inhibitors (INSTIs), and they block integrase strand transfer activity that is required to insert viral DNA into a host cell chromosome. Examples include (generic name shown) raltegravir, dolutegravir and elvitegravir.

REFERENCES

Denyer S.P., Hodges N.A and Gorman S.P (2004). Hugo & Russell’s Pharmaceutical Microbiology. 7th ed. Blackwell Publishing Company, USA. Pp.152-172.

Drusano G.L (2007).  Pharmacokinetics   and   pharmacodynamics   of   antimicrobials.  Clin   Infect   Dis, 45(suppl):89–95.

Ashutosh Kar (2008). Pharmaceutical Microbiology, 1st edition. New Age International Publishers: New Delhi, India.

Axelsen P. H (2002). Essentials of Antimicrobial Pharmacology. Humana Press, Totowa, NJ.

Hardman JG, Limbird LE, eds.  Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001.

Finch R.G, Greenwood D, Norrby R and Whitley R (2002). Antibiotic and chemotherapy, 8th edition. Churchill Livingstone, London and Edinburg.

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