Innovation and trends in the development and approval of antiviral medicines: 1987–2017 and beyond

Abstract

2017 marked the 30th anniversary of the approval of zidovudine (AZT) as the first HIV/AIDS therapy. Since then, more than eighty antiviral drugs have received FDA approval, half of which treat HIV infection. Here, we provide a retrospective analysis of approved antiviral drugs, including therapeutics against other major chronic infections such as hepatitis B and C, and herpes viruses, over the last thirty years. During this time, only a few drugs were approved to treat acute viral infections, mainly influenza. Analysis of these approved antiviral drugs based on molecular class and mode of action shows that a large majority are small molecules and direct-acting agents as opposed to proteins, peptides, or oligonucleotides and host-targeting therapies. In addition, approvals of combination therapies accelerated over the last five years. We also provide a prospective study of future potential antiviral therapies, based on current clinical research pipelines across the pharmaceutical industry. Comparing past drug approvals with current clinical candidates hints at the future evolution in antiviral therapies and reveals how antiviral medicines are often discovered. Overall, this work helps forecast future trends and innovation in the field of antiviral research and development.

Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

“…Even though more than 90 antiviral drugs are currently approved for the treatment of viral infections, many are suitable for use only with a single virus (De Clercq and Li, 2016). New antiviral drugs with activity against multiple viral types are being sought, and many of these compounds are undergoing advanced clinical trials (Chaudhuri et al, 2018). Several of these drugs are used for diseases caused by herpesviruses.…”

“…The introduction of new antiviral agents for clinical use has revolutionized the treatment of many viral infections caused by either DNA or RNA viruses (De Clercq and Li, 2016;De Clercq, 2013a;Chaudhuri et al, 2018). Most of the approved drugs have been licensed for the treatment of infections caused by a single virus.…”

SARS‐CoV‐2: What do we know so far?

“…Currently, there are more than 90 antiviral drugs approved for use in humans. More than half of these are used to treat HIV infections, a third against herpes simplex virus, human cytomegalovirus, varicella zoster virus and influenza, and the remainder for miscellaneous viruses 30,31 . Drug repurposing is, therefore, a frequently applied strategy for developing treatment regimens in situations such as the current outbreak 32,33 …”

Novel Small Molecule Targeting the Hemagglutinin Stalk of Influenza Viruses

“…Antiviral drugs can be another option as universal intervention methods against various (sub)types of influenza viruses (22,23). Most antivirals approved by the Food and Drug Administration are small molecules (24), and several types of antiviral drugs have been used to treat influenza (25). However, due to the possibility of the emergence and dissemination of antiviral-resistant strains (26,27), new types of antivirals are always needed.…”

“…However, due to the possibility of the emergence and dissemination of antiviral-resistant strains (26,27), new types of antivirals are always needed. Nine antiviral drug candidates (baloxavir marboxil, a cap-dependent endonuclease inhibitor [28], which has been licensed recently in the United States; FluDase, a recombinant sialidase fusion protein [29]; JNJ-5806, a polymerase inhibitor; laninamivir octanoate, a neuraminidase inhibitor [30]; MEDI8852, an HA stem-binding monoclonal antibody [31]; NT-300, an HA intracellular trafficking inhibitor; pimodivir, a PB2 cap-snatching inhibitor [32]; radavirsen, a genetic transcription inhibitor of antisense oligonucleotide [33]; and VIS-410, an HA stem-binding monoclonal antibody [34]) are in clinical trials (24), five of which are small molecules that have advantages of standardization and manufacturing processes.…”