Trends and strategies to combat viral infections: A review on FDA approved antiviral drugs

Abstract

The infectious microscopic viruses invade living cells to reproduce themselves, and causes chronic infections such as HIV/AIDS, hepatitis B and C, flu, etc. in humans which may lead to death if not treated. Different strategies have been utilized to develop new and superior antiviral drugs to counter the viral infections. The FDA approval of HIV nucleoside reverse transcriptase inhibitor, zidovudine in 1987 boosted the development of antiviral agents against different viruses. Currently, there are a number of combination drugs developed against various viral infections to arrest the activity of same or different viral macromolecules at multiple stages of its life cycle; among which majority are targeted to interfere with the replication of viral genome. Besides these, other type of antiviral molecules includes entry inhibitors, integrase inhibitors, protease inhibitors, interferons, immunomodulators, etc. The antiviral drugs can be toxic to human cells, particularly in case of administration of combination drugs, and on the other hand viruses can grow resistant to the antiviral drugs. Furthermore, emergence of new viruses like Ebola, coronaviruses (SARS-CoV, SARS-CoV-2) emphasizes the need for more innovative strategies to develop better antiviral drugs to fight the existing and the emerging viral infections. Hence, we reviewed the strategic enhancements in developing antiviral drugs for the treatment of different viral infections over the years.

Keywords: Antiviral drugs; Combination therapies; Entry inhibitors; NNRTIs; NRTIs; Protease inhibitors; Virus pandemics.

Fig. 1

The life cycle of viruses. The virus initially attaches to the host cell receptors via its surface proteins which facilitates its internalization. The internalized virus releases its genome into the cytosol to be replicated (RNA in cytosol and DNA in nucleus), transcribed and translated, to produce essential viral proteins. The viral components assemble together to develop into progeny virions which are released into extracellular space through budding or lysis of host cell.

Fig. 2

Trends in antiviral drugs development. (a) Comparison of number of antiviral drugs developed against different viral diseases since 1960s. Major breakthrough in development of antiviral therapeutics for different viral infections occurred after the emergence of HIV (1991–2020). (b) Among the FDA approved antiviral therapies, majority are small molecules and the smaller fraction oligomeric molecules include proteins, peptides and oligonucleotides. (c) Division of the 118 antiviral therapies based on number of their drug components and target of action. HIV - human immunodeficiency virus, HCV - hepatitis C virus, HBV - hepatitis B virus, Infl - influenza virus, HSV - herpes simplex virus, HPV - human papillomavirus, RSV - respiratory syncytial virus, HCMV - human cytomegalovirus, VZV - varicella-zoster virus.

Fig. 3

Antiviral drugs developed to target different stages of the life cycle of infectious viruses. HIV is targeted at nearly all stages of its multiplication, while viral genome replication and transcription stages of all viruses are targeted to prevent viral replication.