Key Ammo in Fighting the Epidemic: Antiviral Drugs
Amador vigilantly tracks COVID-19 information amid the epidemic period to ensure all staff are well prepared in self-protection regardless of virus outbreak. Amador’s experts leverage the medical expertise and have conducted multiple online trainings on COVID-19 general science and the knowledge of drug development in this area.
Apart from protective vaccines and body’s immunity, we also developed antiviral drugs as the weapon to fight viruses by targeting key steps in the viral life cycle.
01 INTRODUCTION
Why are there so few antiviral drugs?
- Compounds interfering with virus growth can adversely affect the host cell (side effects/every step in viral life cycles engages host functions)
- Target viruses difficult to culture, have no animal model, or require extremely high biosafety level to manipulate (HBV, Smallpox, Ebola)
- FDA requires 2 animal models tested before human trials
- Block virus replication completely to reduce resistance
- Short duration of acute infection for clinical impact evaluation
- Lack of effective diagnostic methods
Evolution of antiviral drug discovery
Trends for 1987-2017
02 MECHANISMS
- Prevention of Viral Entry
- Targeting the RNA/DNA replication in the cell
- Targeting the transcriptase factors for Viral DNA
- Destroying Viral proteases so that viral proteins are not cut and rearranged in optimal order
- Stopping the release of the mature viruses from the host cell
Examples of antiviral mechanism (Entry/fusion inhibitors)
- Bing to receptor or uptake into intercellular vesicles (Maraviroc马拉韦罗)
- -CCR5 receptor antagonist blocks CD4 protein-HIV gp120 binding
- Fusion of viral and host cell membrane (Enfuvirtide恩夫韦肽/大分子)
- -blocks fusion of HIV with the host cell by interacting with gp41
- Palivizumab (帕丽珠单抗/大分子)
- -Against the A antigenic site of the F protein of RSV
- Arbidol (阿比多尔) for 2019-nCoV?
- -prevent Hemagglutinin mediated membrane fusion of influenza
Approved entry/uncoating inhibitors
Examples of antiviral mechanism (Nucleic acid synthesis inhibitors-best type we have )
1. Nucleoside analogue
- Acyclovir (HSV-1, HSV-2 and VZV)
- -a nucleoside analogue
- -a chain terminator: deactivate the enzymes that synthesize the DNA once the analogue is incorporated
- -need viral enzyme; non-toxic to uninfected cells
- Ribavirin (利巴韦林）for 2019-nCoV?
- Zidovudine (齐多夫定 HIV)
- Lamivudine, 3TC (HIV, HBV)
2. Non-nucleoside reverse transcriptase inhibitors (NNRTI): Nevirapine, Delavirdine, Efavirenz for HIV
- *Drug resistance-mutations in the viral reverse transcriptase enzyme.
Approved nucleic acid synthesis inhibitors
Approved NRTIs and NNRTs
Examples of antiviral mechanism (Nucleic acid synthesis inhibitors-best type we have)
Protease inhibitors (Kaletra克立芝: Lopinavir-Ritonavir)
for 2019-nCoV?
- to treat HIV and HCV
- prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Neuraminidase inhibitors (Oseltamivir奥司他韦) for 2019-nCoV?
- to treat influenza A and B
- preventing reproduction by budding from the host cell
Approved protease inhibitors
Approved neuraminidase inhibitors
