scholarly journals A Quinolinone Compound Inhibiting the Oligomerization of Nucleoprotein of Influenza A Virus Prevents the Selection of Escape Mutants

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 337
Author(s):  
Juliann Nzembi Makau ◽  
Ken Watanabe ◽  
Hiroki Otaki ◽  
Satoshi Mizuta ◽  
Takeshi Ishikawa ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Nuclear Export ◽  
Influenza A ◽  
Drug Resistant ◽  
In Silico Screening ◽  
Antiviral Compound ◽  
Escape Mutants ◽  
2009 H1n1 ◽  
Emergence Of Resistance ◽  
Selection Of

The emergence of resistance to currently available anti-influenza drugs has heightened the need for antivirals with novel mechanisms of action. The influenza A virus (IAV) nucleoprotein (NP) is highly conserved and essential for the formation of viral ribonucleoprotein (vRNP), which serves as the template for replication and transcription. Recently, using in silico screening, we identified an antiviral compound designated NUD-1 (a 4-hydroxyquinolinone derivative) as a potential inhibitor of NP. In this study, we further analyzed the interaction between NUD-1 and NP and found that the compound interferes with the oligomerization of NP, which is required for vRNP formation, leading to the suppression of viral transcription, protein synthesis, and nuclear export of NP. We further assessed the selection of resistant variants by serially passaging a clinical isolate of the 2009 H1N1 pandemic influenza virus in the presence of NUD-1 or oseltamivir. NUD-1 did not select for resistant variants after nine passages, whereas oseltamivir selected for resistant variants after five passages. Our data demonstrate that NUD-1 interferes with the oligomerization of NP and less likely induces drug-resistant variants than oseltamivir; hence, it is a potential lead compound for the development of novel anti-influenza drugs.

scholarly journals Triple Combination Antiviral Drug (TCAD) Composed of Amantadine, Oseltamivir, and Ribavirin Impedes the Selection of Drug-Resistant Influenza A Virus

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e29778 ◽  
Author(s):  
Justin D. Hoopes ◽  
Elizabeth M. Driebe ◽  
Erin Kelley ◽  
David M. Engelthaler ◽  
Paul S. Keim ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Drug ◽  
Drug Resistant ◽  
Triple Combination ◽  
Selection Of

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

scholarly journals Attaching Zanamivir to a Polymer Markedly Enhances Its Activity Against Drug-resistant Strains of Influenza a Virus

2011 ◽  
Vol 100 (3) ◽  
pp. 831-835 ◽  
Author(s):  
Alisha K. Weight ◽  
Jayanta Haldar ◽  
Luis Álvarez de Cienfuegos ◽  
Larisa V. Gubareva ◽  
Terrence M. Tumpey ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3315 ◽  
Author(s):  
Ling Luo ◽  
Weili Han ◽  
Jinyan Du ◽  
Xia Yang ◽  
Mubing Duan ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Chenodeoxycholic Acid ◽  
Nuclear Export ◽  
Influenza A ◽  
Antiviral Agent ◽  
Dietary Fats ◽  
Lipid Mediator ◽  
Omega 3 ◽  
Ribonucleoprotein Complexes

Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 μM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections.

scholarly journals A new common mutation in the hemagglutinin of the 2009 (H1N1) influenza A virus

PLoS Currents ◽  
2010 ◽  
Vol 2 ◽  
pp. RRN1162 ◽  
Author(s):  
Sebastian Maurer-Stroh ◽  
Raphael Tze Chuen Lee ◽  
Frank Eisenhaber ◽  
Lin Cui ◽  
Shiau Pheng Phuah ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Common Mutation ◽  
2009 H1n1

scholarly journals Inactivated pandemic 2009 H1N1 influenza A virus human vaccines have different efficacy after homologous challenge in the ferret model

2020 ◽  
Vol 15 (1) ◽  
pp. 142-153
Author(s):  
Beatriz Vidaña ◽  
Sharon M. Brookes ◽  
Helen E. Everett ◽  
Fanny Garcon ◽  
Alejandro Nuñez ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
2009 H1n1 ◽  
Homologous Challenge
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