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

被引:144
作者
Chaudhuri, Shuvam [1 ]
Symons, Julian A. [1 ]
Deval, Jerome [1 ]
机构
[1] Alios BioPharma Inc, San Francisco, CA USA
关键词
Antiviral; Small molecule; Direct acting agent; Chronic viral infection; Respiratory virus; HEPATITIS-C VIRUS; EBOLA-VIRUS; INHIBITOR; POTENT; 1ST-IN-CLASS; RESISTANCE; INFECTION; EFFICACY;
D O I
10.1016/j.antiviral.2018.05.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:76 / 88
页数:13
相关论文
共 44 条
[1]   HIV drug resistance against strand transfer integrase inhibitors [J].
Anstett, Kaitlin ;
Brenner, Bluma ;
Mesplede, Thibault ;
Wainberg, Mark A. .
RETROVIROLOGY, 2017, 14
[2]   Comparing influenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals [J].
Bagga, Bindiya ;
Woods, Christopher W. ;
Veldman, Timothy H. ;
Gilbert, Anthony ;
Mann, Alex ;
Balaratnam, Ganesh ;
Lambkin-Williams, Robert ;
Oxford, John S. ;
McClain, Micah T. ;
Wilkinson, Tom ;
Nicholson, Brad P. ;
Ginsburg, Geoffrey S. ;
DeVincenzo, John P. .
ANTIVIRAL THERAPY, 2013, 18 (06) :785-791
[3]   Discovery of Daclatasvir, a Pan-Genotypic Hepatitis C Virus NS5A Replication Complex Inhibitor with Potent Clinical Effect [J].
Belema, Makonen ;
Meanwell, Nicholas A. .
JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (12) :5057-5071
[4]  
Berke JM, 2017, ANTIMICROB AGENTS CH, V61, DOI [10.1128/aac.00560-17, 10.1128/AAC.00560-17]
[5]   Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector [J].
Burke, Bryan P. ;
Levin, Bernard R. ;
Zhang, Jane ;
Sahakyan, Anna ;
Boyer, Joshua ;
Carroll, Maria V. ;
Colon, Joanna Camba ;
Keech, Naomi ;
Rezek, Valerie ;
Bristol, Gregory ;
Eggers, Erica ;
Cortado, Ruth ;
Boyd, Maureen P. ;
Impey, Helen ;
Shimizu, Saki ;
Lowe, Emily L. ;
Ringpis, Gene-Errol E. ;
Kim, Sohn G. ;
Vatakis, Dimitrios N. ;
Breton, Louis R. ;
Bartlett, Jeffrey S. ;
Chen, Irvin S. Y. ;
Kitchen, Scott G. ;
An, Dong Sung ;
Symonds, Geoff P. .
MOLECULAR THERAPY NUCLEIC ACIDS, 2015, 4 :e236
[6]   Preclinical Activity of VX-787, a First-in-Class, Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit [J].
Byrn, Randal A. ;
Jones, Steven M. ;
Bennett, Hamilton B. ;
Bral, Chris ;
Clark, Michael P. ;
Jacobs, Marc D. ;
Kwong, Ann D. ;
Ledeboer, Mark W. ;
Leeman, Joshua R. ;
McNeil, Colleen F. ;
Murcko, Mark A. ;
Nezami, Azin ;
Perola, Emanuele ;
Rijnbrand, Rene ;
Saxena, Kumkum ;
Tsai, Alice W. ;
Zhou, Yi ;
Charifson, Paul S. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (03) :1574-1587
[7]   FOCUS ON RESEARCH Broadly Neutralizing Antibodies for HIV-1 Prevention or Immunotherapy [J].
Caskey, Marina ;
Klein, Florian ;
Nussenzweig, Michel C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (21) :2019-2021
[8]  
Coates M, 2017, ANTIMICROB AGENTS CH, V61, DOI [10.1128/AAC.00737-17, 10.1128/aac.00737-17]
[9]   Association between daily antiretroviral pill burden and treatment adherence, hospitalisation risk, and other healthcare utilisation and costs in a US medicaid population with HIV [J].
Cohen, Calvin J. ;
Meyers, Juliana L. ;
Davis, Keith L. .
BMJ OPEN, 2013, 3 (08)
[10]   Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants [J].
Das, K ;
Clark, AD ;
Lewi, PJ ;
Heeres, J ;
de Jonge, MR ;
Koymans, LMH ;
Vinkers, HM ;
Daeyaert, F ;
Ludovici, DW ;
Kukla, MJ ;
De Corte, B ;
Kavash, RW ;
Ho, CY ;
Ye, H ;
Lichtenstein, MA ;
Andries, K ;
Pauwels, R ;
de Béthune, MP ;
Boyer, PL ;
Clark, P ;
Hughes, SH ;
Janssen, PAJ ;
Arnold, E .
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (10) :2550-2560