medicinal chemistry of Newly Discovered Antiviral Drugs from 2015-2019

1. Newly Discovered Antiviral
Drugs
By Abera Dessie
1

2. Contents
2
 Antiretroviral therapy
(ART)
 Ibalizumab
 Tenofovir alafenamide
 smallpox diseases
treatment
 Tecovirimat
 Influenza treatments
 Baloxavir Marboxil
 neuraminidase (NA)
inhibitors
 antiHCV
 Ledipasvir
 Grazoprevir
 pibrentasvir

3. ART
3
Ibalizumab
 Anti-CD4 monoclonal antibody for the treatment of HIV-1
infection (HIV patients with MDR)
 interferes with viral entry
 Ibalizumab is a human IgG4 anti-CD4 MAb derived from a
murine MAb
 binding to the interface between domain 1 and domain 2 of
CD4
 Intravenous formulations

4. 4
 The four chains are
stabilized by multiple
disulfide bonds and the
constant region of each
heavy chain has a
single N-linked
oligosaccharide chain.
WWW.fda.gov/clinicalreviews

5. 5
Ming sun et al. front.immunol. 2016

6. 6
 Tenofovir alafenamide
 In 2016 approved for the
treatment of both HIV and
HBV infections
 nucleotide reverse
transcriptase inhibitor and
a prodrug of tenofovir

7. Synthesis
7
Yang et al. Letters in Organic Chemistry, 2018, Vol. 15, No. 1
dicyclohexylcarbodiimide

8. smallpox disease treatment
8
Tecovirimat
 Rx for smallpox disease caused by variola virus.
 MOA inhibits production of extracellular viral forms (viral
protein) , which are responsible for systemic spread of
infection
 It is a tetracyclic acyl hydrazide compound

9. Synthesis
9
cycloheptatriene +
maleic anhydride in
xylenes forms
cycloadduct

10. 10
Tecovirimat inhibits
production of
intracellular enveloped
virus (IEV)
targets the viral p37
protein.
SIGA Technologies, Inc.

11. Baloxavir Marboxil
11
 Treatment for acute uncomplicated influenza
 MOA inhibit viral replication (inhibits mRNA
synthesis)
 is a prodrug that is metabolized to its active form,
baloxavir acid, by esterases in the intestinal lumen

12. BXA binding to influenza A/H1N1 endonuclease
12
Kawai M, et al. Sci Rep. 2018;8: 9633.

13. synthesis
13

14. neuraminidase (NA) inhibitors
14
 The neuraminidase inhibitors (zanamivir, laninamivir,
oseltamivir and peramivir) are potent influenza viral
agents.
 neuraminidase located on the surface of the virus plays
an important role in viral reproduction by contributing to
the release of viruses from infected host cells (sialo
receptor)

15. 15
Laborda et al. Influenza neuraminidase inhibitors: synthetic approaches,
derivatives and biological activity. Molecules. 2016 Nov;21(11):1513.

16. 16
 The 1st NA inhibitor reported was 2,3-Didhydro-2-
deoxy-N-acetylneuraminic acid (DANA).
 The starting material for
all NAI is sialic acid (neu5Ac).
 NA acidic amino sugar
 biological systems
 substrates for neuraminidase

17. 17
Larisa V. Gubareva et al. Antimicrob. Agents Chemother. 2001;

18. HCV replicase inhibitors
18
Ledipasvir
 It is a new drug with a novel mechanism of action
involving the inhibition of non-structural protein 5A
(NS5A), which is an essential component of HCV
replicase

19. Grazoprevir
19
treatment for adults with chronic HCV genotype 1 or 4 infection

20. 20
J. Med. Chem. 2018, 61, 9, 4052-4066

21. pibrentasvir
21
J. Med. Chem. 2018, 61, 9,

22. 22
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